For adults, AML is the most common leukaemia and is characterized by a reduction in normal haematopoietic cells and their replacement by primitive cells. At present, diagnosis is generally achieved by identifying cell immunophenotypes (46–48). Abnormal genetic examination results are recognized as an important prognostic factor. However, accumulating evidence has revealed that some people with normal genetic test results may also have AML (49). Therefore, it is necessary to find new diagnostic markers to screen these patients. Zuo et al. (14) demonstrated that both LINC00963 and MMP15 are upregulated in AML, while miR-608 is reduced. LINC00963 inhibits miR-608 and increases MMP15, which can repress AML cell growth and epithelial to mesenchymal transition (EMT) (14). Interestingly, Zhuang et al. (15) proposed that the lncRNA HOTTIP can upregulate DET1 and DDB1-associated 1 (DDA1) by sponging miR-608. However, the overexpression of DDA1 promotes AML cell proliferation and cell cycle progression (15), which contradicts the research results above. This is because the effector molecules MMP15 and DDA1 have different biological functions. These results remind us that if we want to utilize miRNA as a therapeutic target or diagnostic marker, there may be problems with low specificity.

BCa is one of the most common cancers of the urinary system. The incidence rate of males is higher than that of females (50). BCa causes approximately 150000 deaths worldwide annually (51). Patients with BCa are often admitted to the hospital as an emergency, and the proportion of patients who are actively found through physical examination is not high. In addition, emergency admission often means poor prognosis (52, 53). Therefore, we urgently need to find new diagnostic biomarkers for the early detection of BCa. Liang et al. (11) found that miR-608 is always downregulated in BCa, which accelerates cell proliferation and cell cycle progression. When miR-608 is upregulated, it inhibits the expression of FLOT1 and induces G1 phase arrest via the AKT/FOXO3a signaling pathway. In a xenograft model in vitro, upregulated miR-608 was shown to repress BCa cell proliferation (11). In addition, another team also obtained the same results: overexpression of miR-608 can suppress cell survival and invasion and promote cell apoptosis (54). Therefore, miR-608 seems to have the potential to become a diagnostic marker or therapeutic target.

CRC currently has the fourth highest incidence rate in the world. In recent decades, with the continuous development of screening technology, the incidence rate of CRC has peaked. Early screening is one of the most effective measures to improve the prognosis of CRC patients, so finding new diagnostic markers remains important (55–57). In the past decade, there have been many meta-analyses and studies of the correlation of miR-608 rs4919510 and CRC, but the conclusions have not been consistent. Kupcinskas et al. (58) revealed that in Europe, miR-608 rs4919510 has no association with CRC. Interestingly, another team proposed that miR-608 rs4919510 is related to the risk of CRC in both African Americans and Caucasians (59). Both Dai et al. (60) and Ying et al. (61) further found that miR-608 rs4919510 is associated with decreased risk of CRC, although Gong’s team disagrees (60–62). In addition, Pardini et al. (63) and Xing et al. (64) discovered that miR-608 rs4919510 is related to the prognosis of CRC, specifically, CRC recurrence-free survival (RFS). The rs4919510 variant G allele of miR-608 may upregulate MRPL43 by causing loss of its function, thus promoting CRC cell proliferation, invasion, and migration, inhibiting cell apoptosis, and ultimately increasing the risk of CRC (65). However, in 2018, another study reported that for the Iranian population, miR-608 rs4919510 was not associated with the incidence rate of CRC but was associated with metastatic risk (66). Therefore, we believe that miR-608 is a potential predictive biomarker of CRC.

HCC is the third leading cancer worldwide. The incidence rate of HCC has been high due to the pervasiveness of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Therefore, HCC has caused massive economic costs to human society. It is necessary to find new biomarkers to improve the prognosis of HCC (67–69). Wang et al. (25) found that miR-608 was downregulated in the HCC cell lines HepG2 and SK-Hep-1. Correlation analysis was performed with baseline clinical information. An elevated level of miR-608 was associated with a good prognosis of HCC and was specifically related to tumor size, differentiation, clinical stage, overall survival (OS) and disease-free survival (DFS). Moreover, the researchers also found that miR-608 inhibits its target macrophage migration inhibitory factor (MIF) and promotes cell proliferation (25). Surprisingly, He et al. (24) discovered almost the same pathway, except that the final effector molecule was not MIF but bromodomain-containing 4 (BRD4). This result further confirms that miRNAs can often play a role by targeting multiple targets. If there is synergy between these targets, the specific miRNAs can be considered potential biomarkers. Interestingly, another study revealed that miR-608 rs4919510 is significantly related to good prognosis (long OS) (70). Wang et al. (71) confirmed this conclusion by collecting clinical information from 993 HCC patients and 992 healthy individuals. Therefore, miR-608 has prognostic value and is expected to become a potential therapeutic target for HCC.

Among cancers, the incidence rate of LC is the highest in the world, and the incidence rate of LC in women with a history of smoking is the third highest. LC also has the highest mortality among cancers, and the mortality rates in men and women are both the second highest (72–75). Therefore, it is of great significance to reveal the mechanisms underlying the occurrence and development of LC. In 2016, Li et al. (27) discovered that miR-608 rs4919510 was likely associated with both LC risk and susceptibility to LC. In 2019, Xu et al. (26) revealed that compared with that in normal lung tissue, miR-608 expression was downregulated in LC tissue. A dual-luciferase reporter experiment showed that BRD4 was a direct target of miR-608, and the expression level of BRD4 was upregulated in LC tissues. Reduced miR-608 can also promote LC cell proliferation, migration, and invasion through the JAK2/STAT3 signaling pathway (26). These results confirm the results of a study three years ago. Moreover, miR-608 was also found to be downregulated in non−small-cell lung cancer (NSCLC) by of sequencing samples from 106 NSCLC patients and 124 healthy people. Although miR-608 does not affect the incidence of NSCLC, miR-608 can target transcription factor AP-4 (TFAP4) via the Hippo-YAP signaling pathway, thereby promoting NSCLC cell apoptosis and inhibiting cell proliferation (28, 76). Through the Hippo-YAP signaling pathway, miR-608 can also target TEA domain transcription factor 2 (TEAD2) and increase cisplatin sensitivity in NSCLC (77). Moreover, miR-608 can exert a tumor-protecting function in small‐cell lung cancer (78). What is more surprising is that in LUSC, miR-608 promotes LUAD cell death and increases the antiproliferative effect of gefitinib via the PI3K/AKT, WNT, TGF-β, and ERK signaling pathways (37, 79). Therefore, there is sufficient evidence to indicate that miR-608 is a potential therapeutic target and prognostic biomarker.

Pancreatic cancer has the worst prognosis of solid tumors (80, 81). Pancreatic cancer mortality ranks fourth among cancers worldwide and has risen considerably in the past few years (82, 83). The incidence of pancreatic cancer continues to slowly increase. This trend is because most pancreatic cancers are exocrine cell tumors, and the prognosis for exocrine cell tumors is worse than that of endocrine cell pancreatic cancers. Of exocrine cell tumors, pancreatic ductal adenocarcinomas (PDACs) are the most common subtype (84). Unfortunately, it is very difficult to detect pancreatic cancer early because of the lack of obvious symptoms. Thus, further discovery of new predictive biomarkers is urgently needed. In 2020, Nishiwada et al. (85) successfully constructed a diagnostic model that consisted of 6 miRNAs and had excellent performance in identifying lymph node metastasis in PDAC patients. The success of this model implies that miRNAs can be very valuable in the early diagnosis of pancreatic cancer. Interestingly, in pancreatic cancer, miR-608 is downregulated, and miR-608 can target ribonucleotide reductase M1 (RRM1) and cytidine deaminase (CDA) and control gemcitabine resistance (32). miR-608 also promotes PDAC cell apoptosis and prolongs PDAC patient OS by binding BRD4 (86, 87) and AKT serine/threonine kinase 2 (AKT2). Therefore, miR-608 has the potential to act as a new diagnostic and prognostic marker and even a treatment target for pancreatic cancer.

The incidence rate and mortality rate of esophageal cancer are among the top ten rates of all cancers (88–90). Esophageal adenocarcinoma (EAC) and ESCC are the two major subtypes of esophageal cancer (88). New biomarkers for ESCC are currently a hot topic of research, and miRNAs have already shown some advantages. Liu et al. (36) revealed that in ESCC EC109 and TE-1 cells, miR-608 targets TUSC2, inhibits cell proliferation and invasion, and promotes cell apoptosis. In addition, miR-608 rs4919510 can also act as a predictive factor for ESCC, as proven by bioinformatics methods (91).

In addition to the cancers mentioned above, miR-608 is also reduced in many other cancers. In chordoma, miR-608 is significantly downregulated and interacts with EGFR and Bcl-xL. The downregulation of miR-608 can accelerate chordoma cell proliferation and migration and repress cell apoptosis (17). In addition, miR-608 sponges RAC2/BCL2L1 and promotes prostate cancer cell proliferation, G2/M transition, and migration (33). In addition, miR-608 also exerts a tumor-inhibiting effect in breast cancer (92), clear cell renal cell carcinoma, gastric cancer, glioblastoma (GBM), glioma, head and neck squamous cell carcinoma, rectal cancer, Kaposi’s sarcoma associated with herpesvirus infection, melanoma, nasopharyngeal carcinoma (NPC), neuroblastoma, osteosarcoma, and ovarian cancer ( Table 2 ).

Clinically, in almost all cancers, tumor size is closely related to the prognosis of patients and influences the choice of treatment. Thus, the mechanisms of tumor growth and progression deserve attention. Tumor growth is closely related to the degrees of tumor cell proliferation and apoptosis. Whether a tumor grows often depends on which of these processes is stronger. Increasing evidence shows that miR-608 can significantly inhibit the proliferation of a variety of solid tumors, suggesting that miR-608 is closely related to cell proliferation and apoptosis. Next, we will elaborate the molecular mechanism by which miR-608 is involved in tumor growth from two perspectives.

Membrane proteins are the main executors of biofilm function. They can effectively participate in cell energy exchange, information recognition and transmission and material transport. According to the different positions of membrane proteins in the cell membrane, these proteins can be divided into peripheral membrane proteins and internal membrane proteins, which are also called transmembrane proteins (99). miR-608 can bind to the 3’-UTR of many transmembrane proteins to inhibit cancer cell proliferation and accelerate cell apoptosis. Among these transmembrane proteins, EGFR is especially important because EGFR can interact with epidermal growth factor (EGF) and induce receptor dimerization and tyrosine autophosphorylation, resulting in cell proliferation. Both Liu et al. (42) and Zhang et al. (17) reported that EGFR is a target of miR-608 and that miR-608 can indirectly attenuate cell proliferation by inhibiting EGFR. Moreover, MMP-15, another transmembrane protein, binds to miR-608 and participates in the progression of AML. Furthermore, rescue experiments indicate that overexpression of LINC00963 promotes cell proliferation and EMT by modulating MMP-15 (14). Interestingly, FZD4 is reported to be upregulated in ovarian cancer, and FZD4 is a transmembrane protein that belongs to the β-catenin signaling pathway. Generally, HOXD4-AS1 exerts tumor-promoting functions through the miR-608/FZD4 axis in ovarian cancer (30). These four studies all clearly indicate that the inhibition of transmembrane proteins by miR-608 leads to suppression of cell growth.

miR-608 modulates tumor growth not only by affecting transmembrane proteins but also by affecting multiple signaling pathways. The MAPK pathway has three levels of signal transmission: MAPK, MAPK kinase (MEK or MKK) and kinase of MAPK kinase (MEKK or MKKK). These three kinase levels can be activated in sequence and together regulate a variety of important physiological/pathological effects, such as cell growth and differentiation (100). Importantly, MAPK is also involved in the apoptosis induced by ultraviolet radiation (101). miR-608 targets EGFR and p53 and affects cell cycle processes via the MAPK pathway (42). Interestingly, p53 can further activate the PI3K/AKT pathway and influence the cell cycle and mitosis (102). In addition, miR-608 also affects the AKT/FOXO3a signaling pathway to control cell proliferation. miR-608 inhibits both the AKT and FOXO3a kinases and blocks the signaling pathway to attenuate cell proliferation (11) and accelerate cell apoptosis. Moreover, when miR-608 is overexpressed, the expression levels of BRD4, p-JAK2, p-STATA3, CD44, and MMP9 are significantly decreased, indicating that the JAK2/STAT3 signaling pathway is inhibited by miR-608 (26). The inhibition of miR-608 is essential for tumor suppression.