miRNAs are RNA molecules that are 22 nucleotides in length and regulate gene expression by binding to complementary target messenger RNAs (mRNAs) (Lagos-Quintana et al., 2001). The tissue-specific expression of miRNAs provides a premise for their clinical application as diagnostic and prognostic markers in cancer (Kim and Croce, 2021). For example, miR-574-3p is significantly downregulated in PCa tissues, and low expression of miR-574-3p is associated with an advanced tumor stage and a high Gleason score (Chiyomaru et al., 2013). The interactions between miRNAs and the Wnt signaling pathway in PCa are of two types: direct targeting of key genes associated with the Wnt signaling pathway and indirect targeting of the pathway via other genes. Based on their function, miRNAs can be categorized as oncogenic miRNAs or tumor suppressor miRNAs. Most miRNAs, including miR-34a, miR-34b/c, miR-1297, miR-1271, miR-218, miR-520b, miR-138, miR-574-3p, miR-15a-3p, and miR-320, exert tumor-suppressive effects by directly or indirectly inhibiting the Wnt signaling pathway (Chiyomaru et al., 2013; Hsieh et al., 2013; Liu et al., 2015; Li et al., 2016b; Liang et al., 2016; Zhong et al., 2017; Ren et al., 2018; Yu et al., 2018; Cui et al., 2019; Dong et al., 2020). However, a few miRNAs, such as miR-653-5p, miR-182, miR-1301-3p, and miR-454, promote malignant progression of PCa cells, such as proliferation, invasion, and migration, by activating the Wnt signaling pathway and targeting tumor suppressor genes (Guan et al., 2017; Fu et al., 2018; Wang et al., 2018; Fu et al., 2019). Simultaneously, miRNAs can also suppress stemness in PCa by inhibiting the Wnt signaling pathway (Hsieh et al., 2013; Zhou et al., 2016; Song et al., 2018). For example, miRNAs, such as miR-320 and miR-1301-3p, inhibit the activation of the Wnt signaling pathway and suppress the proliferation of PCa stem cells (Hsieh et al., 2013; Song et al., 2018). In addition, certain naturally active chemical substances have been found to exert therapeutic effects on PCa by regulating miRNAs and the Wnt signaling pathway. For example, urolithin, an active metabolite produced by human colonic microbiota, has been found to inhibit miR-21 and its downstream Wnt signaling pathway, thereby promoting apoptosis of PCa cells and inhibiting tumor growth (Zhou et al., 2016). Therefore, miRNAs and the Wnt signaling pathway may become notable therapeutic targets in PCa treatment, and their in-depth examination may reveal the pathogenesis of PCa and aid in the development of novel drugs against PCa.

LncRNAs are RNA molecules that are 200 nucleotides in length and do not encode proteins (Szaflik et al., 2022). Although most of the genome is comprised of ncRNAs that are encoded by “junk DNA,” they were originally considered to lack physiological functions (Huang et al., 2023). However, as the potential roles of lncRNAs in biological processes have been unveiled, the aforementioned notion has gradually changed (Wang et al., 2022a). LncRNAs regulate gene expression at various levels, i.e., chromatin, transcriptional, and post-transcriptional levels (Bhattacharjee et al., 2023; Petrone et al., 2023). Mounting evidence suggests that lncRNAs play crucial roles in PCa cell invasion, migration, and apoptosis and in castration-resistant PCa (CRPC), thereby affecting the proliferation, migration, and response of cancer cells to treatment (Li et al., 2020d; Song et al., 2020; Liu et al., 2021; Tan et al., 2021; Wu et al., 2021). LncRNAs can serve as signals, baits, or scaffolds to modulate cellular functions (Yang et al., 2020; Yan and Bu, 2021). Similar to miRNAs, lncRNAs may exert tumor-suppressive or oncogenic effects, contingent upon their category and mode of regulation. For example, lncRNAs such as TUG1, SOX2-OT, LINC04080, LINC00115, LINC00689, NORAD, SNHG1, and LEF1-AS1 activate the Wnt signaling pathway and promote tumor growth and metastasis by regulating other ncRNAs or proteins (Wang et al., 2019; Li et al., 2020a; Chen et al., 2020; Meng et al., 2020; Song et al., 2020; Zhang and Li, 2020; Peng et al., 2021). Conversely, lncRNAs such as lncRNA625 and HOTAIRM1 inhibit the Wnt signaling pathway to suppress cancer, promote cell apoptosis, and inhibit cell proliferation in PCa (Li et al., 2017; Wang et al., 2021). Investigation of the role of lncRNA625 in cancers has revealed that it promotes tumor development in esophageal carcinoma; however, it exerts a significant tumor-suppressive effect on PCa, suggesting that lncRNA625 could potentially serve as a therapeutic target for PCa (Li et al., 2017; Guo-Wei et al., 2019). Given the lack of effective PCa treatments, the investigation of treatments based on Wnt signaling pathway-related lncRNAs is of great significance for developing novel therapeutic strategies for PCa. Therefore, in-depth research on lncRNAs is expected to yield novel treatment options for patients with PCa. In addition, Wnt signaling pathway-related lncRNAs may have notable implications for prognosis evaluation and diagnostic positioning for PCa, with diverse potential applications.

CircRNAs were first discovered in plant viruses and the Sendai virus through electron microscopy in 1976 (Kolakofsky, 1976). However, it is a widely held belief that circRNAs are the result of splicing errors and exhibit low expression levels (Memczak et al., 2013). With the advancement of bioinformatics and sequencing technologies, various types of circRNAs have been implicated in tumors (Zhou et al., 2021). For example, cir-znf215 has been found to promote the growth and metastasis of cholangiocarcinoma by inhibiting the AKT pathway (Liao et al., 2023). circRNAs also exhibit tissue- and cell-specific expression (Wang et al., 2023). Therefore, circRNAs could potentially serve as diagnostic and prognostic markers as well as therapeutic targets for PCa. cir-ITCH is typically downregulated in PCa tissues and cell lines compared with normal adjacent tissues and normal RWPE-1 cells, indicating the potential of cir-ITCH as a diagnostic and prognostic marker for PCa (Li et al., 2020c). Moreover, cir-ITCH exerts an anti-cancer effect on PCa by inhibiting the Wnt signaling pathway (Li et al., 2020c). In addition, circRNAs interact with ncRNAs and regulate each other’s expression levels (Li et al., 2020c; Ghafouri-Fard et al., 2021). For example, mutual inhibition of expression has been observed between cir-ITCH and miR-17 in PCa (Li et al., 2020c; Ghafouri-Fard et al., 2021).

Metastasis is the primary cause of most cancer-related deaths (Fares et al., 2020). Invasion and migration are critical steps in the cascade of tumor metastasis (Fares et al., 2020). miR-34a is a key regulatory factor in tumor suppression, modulating the expression of numerous target proteins involved in cell cycle, differentiation, epithelial-to-mesenchymal transition (EMT), and apoptosis, among others, and antagonizing processes such as cancer cell activity, stemness, metastasis, and chemoresistance (Misso et al., 2014). The expression of miR-34a is significantly lower in PCa tissues than in normal tissues (Lichner et al., 2015). The overexpression of miR-34a significantly reduces the proliferation and migration abilities of PCa cell lines, sush as PC3 cells (Lichner et al., 2015) (Figure 3). These effects are achieved by inhibiting the Wnt signaling pathway through the regulation of Wnt1 transcriptional activity (Dong et al., 2020). Notably, bones are the most common site of metastasis in PCa (Coleman et al., 2020). In PCa exhibiting activated Ras signaling, bone metastasis associated with low expression of miR-34a has been observed (Chen et al., 2015). miR-34a knockdown has been observed to induce the expression of TCF7 and BIRC5 by activating the Wnt signaling pathway, thereby promoting cell survival (Chen et al., 2015). These findings suggest that miR-34a could serve as a potential target in the treatment of metastatic PCa.

Li et al. demonstrated that miR-1297 directly targets the 3′-untranslated region of AEG-1 and regulates its mRNA and protein expression levels (Liang et al., 2016). In addition, they found that miR-1297 inhibits the Wnt signaling pathway by targeting AEG-1 in PCa, thereby suppressing cell proliferation and invasion (Liang et al., 2016). DIXDC1 is involved in the regulation of the proliferation and invasion of various tumors (Zhong et al., 2017; Xin et al., 2018). In PCa, it can be directly targeted and inhibited by miR-1271 (Zhong et al., 2017). MiR-1271 exhibits low expression in PCa and inhibits cell proliferation, invasion, and Wnt signal transduction by targeting DIXDC1 (Zhong et al., 2017).

Epidemiological and histopathological evidence suggests a correlation between inflammation and PCa incidence (De Nunzio et al., 2011). LGR4, which is induced by IL-6 during cancer progression, has been recently identified as a response gene associated with PCa progression (Liu et al., 2013). Yang et al. found that miR-218 directly targets LGR4 to inhibit the Wnt signaling pathway in LNCaP-IL-6⁺ cells during IL-6-induced PCa cell progression, thereby suppressing cell proliferation, cell cycle progression, and invasion (Li et al., 2016b). CapnS1 has been found to have a negative correlation with disease progression in various solid tumors (Zheng et al., 2020). In PCa, CapnS1 expression is regulated by miR-520b, and it exerts an oncogenic effect by promoting Wnt signal transduction (Ren et al., 2018). miR-520b is significantly downregulated in PCa (Ren et al., 2018). Inhibition of CapnS1 by miR-520b suppresses the growth and invasion of PCa cells associated with the downregulation of Wnt signal transduction (Ren et al., 2018). miR-138 has been observed to be downregulated in invasive PCa cell lines and promote PCa cell invasion and migration through the Wnt signaling pathway, whereas its overexpression has been observed to suppress these functions (Yu et al., 2018). miR-574-3p is significantly downregulated in PCa, and its low expression is associated with advanced tumor stage and a high Gleason score (Chiyomaru et al., 2013). The overexpression of miR-574-3p significantly inhibits the proliferation, migration, and invasion of PCa cells, which is associated with the inhibition of the Wnt signaling pathway via RAC1 (Chiyomaru et al., 2013). SOX30 is a recently identified cancer-related member of the SOX family that has a significant role in various types of cancer (Fu et al., 2019). miR-653-5p is highly expressed in PCa tissues and promotes the proliferation and invasion of PCa cells by targeting and upregulating β-catenin expression via SOX30 and activating the Wnt signaling pathway (Fu et al., 2019). miR-182 expression is higher in PCa tissues than in non-cancerous tissues, and miR-182 significantly activates the Wnt signaling pathway by targeting multiple negative regulators of Wnt signaling, thereby promoting cell proliferation, colony formation, migration, and invasion (Wang et al., 2018). miR-454 is highly expressed in PCa tissues and cell lines and promotes PCa cell proliferation and invasion by upregulating the Wnt signaling pathway, which is achieved by inhibiting NDRG2 expression (Wei et al., 2020). miR-744 significantly activates the Wnt signaling pathway by targeting multiple negative regulators of the pathway and promotes PCa cell proliferation, migration, and invasion (Guan et al., 2017).

TUG1, a 7.1 kb lncRNA, was first discovered to be upregulated in mouse retinal cells in response to taurine treatment (Young et al., 2005). TUG1 is highly expressed in PCa tissues and cells and promotes cell proliferation, migration, and invasion through the miR-496/Wnt/β-catenin axis (Li et al., 2020b; Xiu et al., 2020). LncRNA SOX2-OT plays crucial roles in psychiatric disorders, cancer, and diabetic complications (Li et al., 2020c). In PCa tissues and cells as well, SOX2-OT is highly expressed. Regulation of the miR-452-5p/HMGB3 axis and inactivation of the Wnt signaling pathway have been shown to inhibit PCa cell proliferation and metastasis, thereby suppressing tumor growth in vivo (Song et al., 2020). SNHG12, also known as LINC04080, is a lncRNA spanning approximately 1867 nucleotides and is located in the 1p35.3 region (Lan et al., 2017). In PCa, SNHG12 expression is upregulated in serum and tissues and is associated with RFS, biochemical recurrence, and Gleason scores of 8–10 in patients (Wang et al., 2019). This lncRNA activates the Wnt signaling pathway through the sponging effect of miR-195, thereby promoting cell proliferation, invasion, and migration in PCa (Song et al., 2019). LINC00115 was first identified as a notable pro-cancer lncRNA in lung cancer (Li et al., 2016a). In PCa, it is highly expressed in tissues and closely associated with a poor prognosis (Peng et al., 2021). LINC00115 promotes PCa cell proliferation and invasion by targeting the miR-212-5p/FZD5/Wnt axis (Peng et al., 2021). LINC00689, first found to be associated with obesity susceptibility genes in the Han Chinese population of northern China, exerts a pro-cancer effect in multiple solid tumors, including gastric cancer, breast cancer, and liver cancer (Liu et al., 2019b; Du et al., 2020; Lu et al., 2020). This lncRNA activates the Wnt signaling pathway by regulating miR-496/CTNNB1, thereby promoting PCa cell proliferation, migration, and invasion (Meng et al., 2020). LEF1 is a key component of the Wnt/β-catenin signaling pathway. It is highly expressed in PCa and is associated with its malignant progression (Fakhr et al., 2021). The recently identified lncRNA LEF1-AS1 is encoded by the LEF1 locus and is associated with poor prognosis in multiple cancer types (Li et al., 2020d). LEF1-AS1 promotes PCa metastasis and serves as a competing endogenous RNA (ceRNA) for miR-328, thereby modulating Wnt/β-catenin pathway activity by regulating FZD2 and CD44, ultimately promoting androgen-independent PCa (AIPC) cell proliferation, migration, invasion, angiogenic ability, and tumor growth (Li et al., 2020d). In addition, lncRNAs also play crucial roles in PCa metastasis by directly binding to EZH2 (Chen et al., 2020). For example, both the lncRNAs SNHG1 and EZH2 are highly expressed in PCa tissues and cells, and their expression is positively correlated. SNHG1 regulates the Wnt signaling pathway through the EZH2 gene, modulating PCa cell proliferation, invasion, and migration (Chen et al., 2020). These findings further enrich our understanding of the mechanism of action of Wnt signaling pathway-related lncRNAs in PCa. The aforementioned lncRNAs are associated with the Wnt signaling pathway and play vital roles in the growth and progression of PCa, thereby presenting as novel targets for PCa treatment.

In addition to the aforementioned Wnt signaling pathway-related lncRNAs, the role of the lncRNA CCAT2 in PCa metastasis should be considered (Zheng et al., 2016; He et al., 2020). Studies have shown that complex feedback loops exist between CCAT2 and the Wnt signaling pathway (Zheng et al., 2016; He et al., 2020). Moreover, CCAT2 plays a key role in the invasion and migration of PCa (Zheng et al., 2016; He et al., 2020). Notably, CCAT2 is not only aberrantly expressed in PCa but also exhibits similar expression patterns in many other cancers (Ling et al., 2013). In colorectal cancer, it is a downstream target of the Wnt signaling pathway, indicating that TCF7L2 is also involved in this feedback loop (Ling et al., 2013). Therefore, an in-depth investigation of the role of lncRNAs in the Wnt signaling pathway is of great significance for the prognosis and treatment of cancer as well as the recovery from cancer. In summary, the key role of the lncRNA CCAT2 in PCa metastasis indicates its potential as a therapeutic target.

In contrast to miRNAs and lncRNAs, circRNAs associated with the Wnt signaling pathway in PCa have been the subject of comparatively less investigation. The expression of cir-ITCH is downregulated in PCa tissues and cell lines (Li et al., 2020c), and its overexpression significantly inhibits the proliferation, migration, and invasion of human PCa cells. Cir-ITCH and miR-17 function as mutual expression inhibitory factors (Li et al., 2020c). Cir-ITCH contributes to the suppression of PCa progression by inhibiting the Wnt/β-catenin signaling pathway, which may be achieved through the inhibition of miR-17 (Li et al., 2020c).

The metastasis of solid tumors is also influenced by the characteristics and plasticity of cancer cells, such as EMT (Babaei et al., 2021). During EMT, epithelial cells transform into highly mobile mesenchymal cells, thereby increasing the migration ability of cancer cells (Hao et al., 2019). Inhibiting EMT is key to preventing cancer metastasis and improving prognosis (Fedele et al., 2022). miR-15a-3p is downregulated in PCa tissues and cell lines, whereas its overexpression inhibits cell proliferation, invasion, and EMT by downregulating the Wnt signaling pathway, with SLC39A7 as its direct downstream target (Cui et al., 2019) (Figure 4). LEF1 is a key transcription factor in the Wnt signaling pathway that regulates cell proliferation and invasion (Fakhr et al., 2021). miR-34a can regulate the level of LEF1 to inhibit EMT in PCa cells (Liang et al., 2015). Additionally, two other members of the miR-34 family, namely miR-34b/c, when overexpressed, can target β-catenin mRNA expression, thereby inhibiting cell migration and EMT in PCa (Liu et al., 2015).

The lncRNA NORAD exerts a pro-cancer effect in melanoma, pancreatic cancer, and glioblastoma (Soghli et al., 2021). In PCa as well, NORAD is highly expressed in cells and tissues and promotes cell proliferation, invasion, and EMT (Zhang and Li, 2020; Hu et al., 2021; Fletcher et al., 2022). miR-30a-5p attenuates NORAD-mediated promotion of cell proliferation, invasion, and EMT by targeting RAB11A (Zhang and Li, 2020).

Cell apoptosis is a key self-regulation mechanism in multicellular organisms, serving to eliminate unwanted or abnormal cells (Kerr et al., 1972). Dysregulation of cell apoptosis has been implicated in various diseases, including cancer, autoimmune diseases, cardiovascular diseases, and neurological diseases (Chen et al., 2021). In recent years, a growing body of evidence has shown that ncRNAs play a crucial role in PCa cell apoptosis (Tamtaji et al., 2021). The Wnt signaling pathway is associated with PCa cell apoptosis, and ncRNAs associated with this pathway also play key roles in PCa cell apoptosis (Tamtaji et al., 2021). The overexpression of miR-34a inhibits the Wnt signaling pathway by regulating the transcriptional activity of Wnt1, thereby significantly increasing the rate of cell apoptosis (Dong et al., 2020) (Figure 4). Compared with non-cancerous tissues, PCa tissues exhibit upregulated expression of miR-182 (Wang et al., 2018). The upregulation of miR-182 activates the Wnt signaling pathway by targeting negative regulatory factors of the pathway, such as GSK3β, APC, CK1, and Axin, ultimately inhibiting cell apoptosis (Wang et al., 2018). Urolithin, a bioactive metabolite derived from ellagic acid, has been observed to inhibit miR-21 and its downstream Wnt/β-catenin signaling pathway to reduce cell viability and promote caspase-dependent cell apoptosis in DU145 cells (Zhou et al., 2016; Singh et al., 2019).

LINC0689 exerts a pro-oncogenic effect in multiple parenchymal tumors, where its expression is elevated (Liu et al., 2019b; Du et al., 2020). LINC00689 is upregulated in end-stage PCa tissues and inhibits apoptosis through miR-496/CTNNB1 (Meng et al., 2020). In addition, the lncRNA HOTAIRM1 is highly expressed in mature bone marrow cells (Zhang et al., 2014). Silencing HOTAIRM1 in PC3 cells promotes PCa cell apoptosis by downregulating the Wnt/β-catenin signaling pathway; however, the exact mechanism remains unknown (Wang et al., 2021).

Cancer stem cells play a crucial role in the survival, proliferation, metastasis, and recurrence of tumors (Murota et al., 2022). miR-320 inhibits the activation of the Wnt/β-catenin signaling pathway by targeting β-catenin mRNA expression, thereby suppressing PCa stem cell characteristics such as tumor sphere formation, chemoresistance, and tumorigenicity (Hsieh et al., 2013) (Figure 4). In contrast, miR-320 knockdown significantly enhances the aforementioned characteristics (Hsieh et al., 2013). miR-1301-3p is significantly upregulated in PCa cells and tissues and targets inhibitors of the Wnt signaling pathway, namely GSK3β and SFRP1, thereby promoting the proliferation of PCa stem cells by activating the Wnt/β-catenin signaling pathway (Song et al., 2018).

Targeting the Wnt/β-catenin signaling pathway may be an attractive therapeutic strategy for treating CRPC (Shafi et al., 2013). The potential of Wnt signaling pathway-related lncRNAs in the treatment of CRPC is currently gaining increasing attention (Yap et al., 2011) (Figure 4). Androgen deprivation therapy has become the mainstay for the treatment of patients with advanced PCa (Shafi et al., 2013). However, most patients eventually progress to CRPC, leading to poor prognosis (Yap et al., 2011). Bone metastasis is a notable issue in patients with CRPC (Beltran et al., 2016; Lin et al., 2020). Luo et al. elucidated that crosstalk between the AR and Wnt/β-catenin signals promotes the androgen-independent transformation of PCa (Luo et al., 2020). Although androgens can inhibit the Wnt/β-catenin signaling pathway in androgen-dependent PCa cells, this inhibitory effect is not observed in AIPC cells (Luo et al., 2020). Moreover, LEF1-AS1 has been observed to promote PCa metastasis through the Wnt/β-catenin signaling pathway and function as a ceRNA for miR-328, thereby regulating the activity of the Wnt/β-catenin signaling pathway by regulating FZD2 and CD44, ultimately enhancing proliferation, migration, invasion, and angiogenic ability of AIPC cells and tumor growth (Li et al., 2020d). The Wnt/β-catenin signaling pathway inhibits AIPC cell proliferation by promoting the cell cycle process and inhibiting apoptosis (Luo et al., 2020). Therefore, targeting the Wnt/β-catenin signaling pathway may be a viable strategy for the treatment of CRPC.

Exosomes are small vesicles that measure approximately 40–160 nm (typically approximately 100 nm) in diameter and originate from endosomes (Pegtel and Gould, 2019). Many studies have demonstrated the importance of several lncRNAs in exosomes across various cancers (Kalluri and LeBleu, 2020). For example, the exosomal lncRNA HOXD-AS1 has been observed to promote the metastasis of PCa through the miR-361-5p/FOXM1 axis (Jiang et al., 2021). Wnt signaling pathway-related lncRNAs loaded in exosomes could potentially serve as diagnostic and therapeutic tools for the treatment of CRPC (Guo et al., 2022). For example, LINC01213 plays a role in the transition of PCa cells from an androgen-dependent to an androgen-independent state (Guo et al., 2022). Additionally, it induces androgen deprivation tolerance by activating the Wnt signaling pathway through exosome-mediated intercellular communication in PCa (Guo et al., 2022). The lncRNA SNHG17 is one of the four significantly upregulated lncRNAs in metastatic PCa and AIPC cells, wherein it promotes tumor cell proliferation, survival, invasion, and resistance to chemotherapy by upregulating the Wnt/β-catenin signaling pathway (Bai et al., 2020; Zhao et al., 2021).

Early screening and diagnosis of cancer are crucial for patient survival (Sung et al., 2021). The identification of suitable biomarkers has consistently posed a notable challenge in the field of cancer research (Movahedpour et al., 2022; Xie et al., 2022). Wnt signaling pathway-related ncRNAs aid in the early diagnosis of PCa. In patients with PCa, certain Wnt signaling pathway-related ncRNAs, such as SNHG17 and LINC00115, are upregulated (Peng et al., 2021), whereas other ncRNAs, such as miR-34a, are downregulated (Chiyomaru et al., 2013). Additionally, certain ncRNAs are aberrantly expressed in various stages or special subtypes of PCa (Li et al., 2020d; Meng et al., 2020). For instance, LINC00689 is upregulated in end-stage PCa tissues and LEF1-AS1 is significantly overexpressed in AIPC (Li et al., 2020d; Meng et al., 2020). These findings suggest that Wnt signaling pathway-related ncRNAs could potentially serve as diagnostic biomarkers for PCa. Notably, ncRNAs present in plasma will be relatively non-invasive and more convenient as diagnostic tools. Wnt signaling pathway-related lncRNAs loaded in exosomes could also potentially serve as diagnostic and therapeutic tools for PCa (Guo et al., 2022). For example, exosomal LINC01213 can serve as a diagnostic biomarker for CRPC (Guo et al., 2022).

Patient prognostic information is essential in the process of making informed treatment decisions (Lin and Farooqi, 2021). Mounting evidence suggests that the Wnt signaling pathway-related ncRNAs may hold significant potential for predicting patient prognosis (Chiyomaru et al., 2013; Dong et al., 2020; Xiu et al., 2020; Peng et al., 2021; Zhao et al., 2021). These ncRNAs are closely associated with overall survival, disease-free survival, recurrence-free survival, five-year survival rates, and progression-free survival of patients with PCa (Peng et al., 2021). For example, high expression of LINC00115 is associated with shorter overall survival and recurrence-free survival in patients with PCa (Peng et al., 2021). Additionally, Wnt signaling pathway-related ncRNAs are also associated with other prognostic factors (Chiyomaru et al., 2013; Dong et al., 2020; Xiu et al., 2020; Zhao et al., 2021). For instance, miR-34a is associated with bone metastasis of Ras-activated PCa cells (Dong et al., 2020). Furthermore, miR-574-3p is associated with advanced tumor stage and higher Gleason scores (Chiyomaru et al., 2013). In contrast, high expression of SNHG17 is associated with grade, stage, and metastasis (Zhao et al., 2021). Additionally, TUG1 is associated with Gleason score, clinical stage, preoperative PSA level, and lymph node metastasis (Xiu et al., 2020). These findings have crucial implications for the prognostic assessment and treatment selection in PCa. Therefore, Wnt signaling pathway-related ncRNAs could potentially serve as vital indicators for the prognostic evaluation and treatment selection in PCa.

Cancer treatment has long been regarded as one of the most formidable challenges worldwide, despite the progress made in treatment modalities (Sung et al., 2021). Targeted therapy strategies based on ncRNAs have yielded novel insights into cancer treatment (Paunovska et al., 2022). NcRNAs regulate cell proliferation, invasion, migration, apoptosis, and stemness in PCa and conversion of PCa to CRPC by directly or indirectly interacting with the Wnt signaling pathway (Guan et al., 2017; Wang et al., 2018). Therefore, modulating the expression of Wnt signaling pathway-related ncRNAs could be an effective strategy for treating PCa and improving patient prognosis. For example, silencing miR-182 using inhibitors has been observed to significantly reduce the growth of PCa xenograft tumors, whereas silencing miR-744 using short hairpin RNA (shRNA) has been observed to significantly reduce the growth of PCa xenograft tumors (Guan et al., 2017; Wang et al., 2018). However, identifying targeted drugs that modulate ncRNA expression and stably transmit this effect remains a challenge, and necessites an enhanced understanding of the structure and function of Wnt signaling pathway-related ncRNAs. Most lncRNAs and circRNAs function as “sponges” for miRNAs to activate or deactivate the Wnt signaling pathway (Li et al., 2020d). Therefore, the regulation of target miRNA of Wnt signaling pathway-related lncRNA and circRNA or the interfering with upstream lncRNA and circRNA associated with Wnt signaling pathway-related miRNA could also be a viable treatment strategy. For example, miR-496 intervention has been observed to effectively reverse the growth-promoting effect of TUG1 on PCa xenografts (Li et al., 2020d).

Targeting ncRNAs has been considered an attractive strategy for cancer treatment (Damase et al., 2021; Garbo et al., 2022; Zogg et al., 2022). In addition to using the above approach, there are other methods that can be employed to intervene in the expression of ncRNAs involved in the Wnt pathway, which may provide therapeutic benefits for patients (Damase et al., 2021; Garbo et al., 2022; Zogg et al., 2022). In the field of Wnt pathway-related miRNAs, miRNA mimics (miRNA-like dsRNA) have been found to enhance the expression and function of certain miRNAs; meanwhile, antagomiRs can serve as tools to inhibit oncogenic miRNAs associated with the Wnt pathway, thereby blocking the specific functions of these miRNAs (Neumeier and Meister, 2020; Xu et al., 2023). In recent years, strategies based on lncRNAs for cancer treatment have gained widespread recognition. Currently, the main therapeutic approaches for managing lncRNAs involve modulating their expression levels to decrease oncogenic lncRNAs (through RNA interference methods) or increase tumor-suppressive lncRNAs (Garbo et al., 2022). It is worth noting that targeting strategies for lncRNAs need to take into account their cellular localization. Antisense oligonucleotides (ASOs) are the most effective method for targeting nuclear lncRNAs (Adewunmi et al., 2023). However, small interfering RNAs (siRNAs) are preferred for cytoplasmic lncRNAs (Li et al., 2022). Additionally, other strategies such as aptamers, nucleases, and miRNAs can be developed to disrupt lncRNA activit (Damase et al., 2021; Zogg et al., 2022). Due to their wide biological activity and stability, circRNAs have emerged as a potential and powerful therapeutic strategy that can significantly impact cancer occurrence and progression (Zong et al., 2023). However, limiting off-target effects remains a challenge in this field (Loan Young et al., 2023). Addressing this issue, specific carriers for synthetic circRNAs or siRNAs targeting junction sequences could offer substantial benefits to patients. All in all, targeted therapeutic strategies based on ncRNAs hold promise as a novel approach for PCa treatment.

Chemoresistance is a notable concern in cancer treatment, and enhancing chemosensitivity in PCa through ncRNA intervention has become a strategy that is increasingly being recognized and investigated (Chen et al., 2022). Targeting Wnt signaling pathway-related ncRNAs may help reverse chemoresistance in PCa (Liu et al., 2019a). Cisplatin, a platinum-based chemotherapeutic drug commonly used in the treatment of PCa, works by forming covalent bonds with DNA, leading to the formation of DNA cross-links and inhibiting DNA replication and transcription (Li et al., 2021). In PCa, cisplatin plays a role in inhibiting tumor growth by damaging the DNA of cancer cells and triggering apoptosis (programmed cell death) (Dhar et al., 2011). However, the development of resistance to cisplatin remains a major challenge in PCa treatment. Mechanisms underlying cisplatin resistance in PCa include enhanced DNA repair mechanisms, altered drug uptake and efflux, increased drug inactivation, and alterations in cell death pathways (Kalathil et al., 2023). miR-425-5p is downregulated in PCa and is further downregulated in cisplatin-resistant PCa (Liu et al., 2019a). Therefore, upregulating miR-425-5p by targeting the Wnt signaling pathway could potentially enhance the sensitivity of PCa to cisplatin (Liu et al., 2019a). Additionally, HOTTIP, a known oncogene, is upregulated in patients with PCa and PCa cell lines, promoting PCa cell proliferation and reducing sensitivity to cisplatin by activating the Wnt signaling pathway (Jiang et al., 2019). As a member of a class of chemotherapy drugs known as taxanes, docetaxel acts by disrupting microtubule dynamics, ultimately inhibiting cell division and inducing cell death (Sanchez-Hernandez et al., 2023). Docetaxel exerts its anti-cancer effects by targeting rapidly dividing cancer cells, inhibiting tumor growth, and promoting cancer cell death (Sanchez-Hernandez et al., 2023). In the treatment of PCa, docetaxel is particularly effective in advanced or metastatic CRPC (Gebrael et al., 2023). However, similar to cisplatin, resistance to docetaxel of PCa can develop over time. Mechanisms of docetaxel resistance in PCa involve alterations in microtubule dynamics, activation of cell survival pathways, and increased drug efflux (Gebrael et al., 2023). SNHG17 promotes chemotherapeutic resistance to docetaxel in PCa tumor cells by upregulating the Wnt signaling pathway, thereby leading to increased chemoresistance (Zhao et al., 2021). Therefore, modulation of Wnt signaling pathway-related ncRNAs may be an effective strategy to reverse chemoresistance in PCa. However, identifying targeted drugs that can regulate ncRNA expression and stably transmit this effect remains a challenge (Jaiswal et al., 2023). Therefore, an enhanced understanding of the structure and function of Wnt signaling pathway-related ncRNAs can aid the development of novel treatment strategies to reverse chemoresistance in PCa.