Long non-coding RNAs (lncRNAs) are RNA molecules longer than 200 nucleotides that do not encode proteins (1–4). Initially considered “junk” RNA, they are now recognized as crucial players in human diseases (5–7), particularly cancer (8–10). LncRNAs are classified based on their proximity to protein-coding genes, including sense, antisense, intronic, bidirectional, or intergenic types (11–13). Mechanistically, one of the main functions of lncRNAs involves the ceRNA network (14–16). Acting as “sponges” for microRNAs (miRNAs), lncRNAs bind to miRNAs and modulate their availability for target mRNAs, thereby indirectly regulating gene expression. Disruptions in the ceRNA network involving lncRNAs are evident in various cancers (17–19). Accumulating evidence underscores the pivotal role of lncRNAs in cancer development and progression, highlighting their potential as targets for innovative therapeutic strategies (20–22).

Homo sapiens (human) Long Intergenic Non-Protein Coding RNA 1123 (LINC01123) is classified as a lncRNA gene located on chromosome 2q13. Spanning a length of 8302 nucleotides (nt), this gene comprises four exons (https://www.ncbi.nlm.nih.gov/gene/440894). The LINC01123 gene produces two splice variants: ENST00000419296.1, which is 2436 base pairs (bp) long, and ENST00000336905.3, which spans 2271 bp (Source: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000204588;r=2:109987063-109996140). LINC01123 has recently emerged as a key player in the pathogenesis of various diseases, including deep vein thrombosis (23), atherosclerosis (AS) (24), and acute cerebral infarction (25). Notably, its role in cancer progression has sparked considerable interest (26–28). LINC01123 is upregulated in a wide array of human tumors, and elevated expression levels of LINC01123 in cancerous samples correlate with adverse clinicopathological features and poor prognosis, including lymph node metastasis, tumor size, clinical stage, overall survival (OS), disease-free survival (DFS), and biochemical recurrence (BCR)-free survival. Furthermore, LINC01123 plays a critical role in crucial biological processes such as epithelial-mesenchymal transition (EMT), tumor cell growth, and invasion. Given its pivotal role in tumor progression, LINC01123 is expected to serve as a valuable tumor biomarker and contribute to the development of effective therapeutic strategies across various malignancies.

In this work, we provide a comprehensive summary of the latest research on the roles of LINC01123 in tumor development. We focus on LINC01123 expression patterns, associated clinical characteristics, its potential as a cancer biomarker, and its biological functions in tumor progression. Additionally, we examine the underlying mechanisms driving LINC01123’s effects in various malignancies. This review highlights the promising prospects of LINC01123 as a target for therapeutic interventions in different cancer types.

Recently identified as an oncogenic lncRNA, LINC01123 demonstrates significant upregulation across multiple cancer types originating from various organ systems (26–37). These include cancers of the nervous system (glioma) (29), respiratory system (lung cancer, LC) (28, 30), head and neck region (oral squamous cell carcinoma, OSCC; head and neck squamous cell carcinoma, HNSCC) (26, 27), digestive system (hepatocellular carcinoma, HCC; colorectal cancer, CRC; intrahepatic cholangiocarcinoma) (31–35), and reproductive system (ovarian cancer, OC; cervical cancer, CC) (36, 37), as summarized in Table 1 .

Research has investigated the relationship between LINC01123 expression and clinicopathological features across various cancer types (see Table 1 ). In OSCC, elevated expression of LINC01123 is associated with lymph node metastasis and advanced TNM stage (26). In non-small cell lung cancer (NSCLC), LINC01123 expression is significantly related to TNM stages, T stage, and lymph node metastasis (28). In HCC, increased levels of LINC01123 indicate larger tumor size, venous infiltration, and advanced TNM stage (31). In CRC, higher LINC01123 expression is observed in patients with advanced TNM stage and lymph node metastasis (32). Similarly, in CC, LINC01123 shows a significant positive correlation with lymph node metastasis and higher International Federation of Gynecology and Obstetrics (FIGO) stage (37). Additionally, high LINC01123 expression correlates highly with shorter OS in patients with OSCC (26), HNSCC (27), NSCLC (28), and HCC (31). And high LINC01123 expression levels are associated with worse OS and DFS in CRC patients (32), and LINC01123 is negatively associated with BCR-free survival in prostate cancer (38).

Research has shown that the expression of LINC01123 is regulated by multiple key transcription factors across various tumors ( Figure 1 ) (28, 39, 40). In triple-negative breast cancer (TNBC), LINC01123 is transcriptionally amplified by FOXC1, which directly binds to the LINC01123 promoter and promotes malignant cellular processes in tumor cells (39). This regulatory mechanism suggests that targeting FOXC1 or its interaction with LINC01123 could potentially disrupt tumor progression in TNBC. In lung cancer, studies demonstrate that ZEB1 binds to the LINC01123 promoter regions, initiating transcription and upregulating LINC01123 (40). This upregulation enhances malignant functions in lung adenocarcinoma (LUAD) cells through the miR-449b-5p/NOTCH1 axis, highlighting the potential of targeting this pathway to suppress LUAD progression. Additionally, the transcription factor c-Myc also induces LINC01123 expression, functioning as an oncogene by promoting proliferation and aerobic glycolysis in NSCLC through the miR-199a-5p/c-Myc feedback loop (28). These findings collectively underscore the critical role of transcription factors in regulating LINC01123 and suggest that disrupting these regulatory networks could offer novel therapeutic strategies for multiple cancer types.

Recent studies have extensively examined the role of LINC01123 across eleven different types of tumors, including glioma (29), OSCC (27), HNSCC (27), TNBC (39), NSCLC (28), LUAD (30, 40, 41), HCC (31), CRC (32–34, 42), OC (36), CC (37) and osteosarcoma (43). These investigations highlight the multifaceted role of LINC01123, as evidenced by various in vivo and in vitro experiments summarized in Table 2 .

A consistent finding across these studies is the elevated expression of LINC01123 in numerous tumor cell lines. This observation suggests that LINC01123 could serve as a potential biomarker for tumor aggressiveness, providing an avenue for further research into its prognostic value. At the subcellular level, LINC01123 predominantly localizes to the cytoplasm in six types of cancer cells: colon cancer (32, 34), breast cancer (39), HNSCC (27), LUAD (30, 40), NSCLC (28), glioma (29). This cytoplasmic localization is crucial, as it implicates LINC01123 in the regulation of cytoplasmic processes, including interaction with microRNAs and other cellular components.

The oncogenic role of LINC01123 in tumorigenesis and development is multifaceted, influencing a variety of biological processes (see Figure 2 ). Notably, LINC01123 has been implicated in promoting EMT, which facilitates the metastatic capacity of tumors. By enhancing cell proliferation and inhibiting apoptosis, LINC01123 effectively increases cell viability, thereby supporting tumor growth. Moreover, LINC01123 facilitates not only cell migration and invasion but also induces a stem-like phenotype associated with tumor-initiating properties. This shift towards stemness suggests that LINC01123 may contribute to tumor recurrence and treatment resistance, as cancer stem cells are often implicated in these phenomena. Furthermore, LINC01123 promotes metabolic reprogramming and immune escape, thereby enabling tumors to thrive in hostile environments. This capability underscores the potential for targeted therapies that could disrupt LINC01123 interactions, rendering tumors more susceptible to immune responses and conventional treatments. Lastly, LINC01123’s involvement in angiogenesis and therapy resistance further highlights its critical role in sustaining tumor growth and resilience against treatment. Given these implications, LINC01123 emerges as a promising target for future therapeutic strategies aimed at combating a variety of cancers.

A huge amount of evidence recent suggested that lncRNAs play a vital role in the development of human diseases (60–62). Further investigation into different lncRNAs in human cancers, particularly their involvement in both the onset and advancement of tumors, is valuable and warrants exploration and consolidation. Here, we comprehensively examine current research the clinical values and roles of LINC01123 in human tumors and provides insights into its molecular regulatory mechanisms.

LINC01123, a newly identified lncRNA, consistently exhibits upregulation in various cancerous tissues and cell lines (26–38), suggesting its potential as an oncogene in tumorigenesis. Similarly, overexpression of LINC01089 is associated with advanced clinicopathological features across different cancer types (26, 28, 31, 32, 37), including larger tumor size, lymph node metastasis, and higher TNM stage. Elevated levels of LINC01089 also correlate with poorer prognosis (26–28, 31–33, 38), leading to shorter overall survival and accelerated cancer progression. Thus, LINC01123 serve as a promising prognostic biomarker in multiple tumors.

Recent experimental investigations have characterized the functional roles of LINC01123 across eleven distinct cancer types ( Table 2 ), including glioma (29), OSCC (27), HNSCC (27), TNBC (39), LUAD (30, 40, 41), NSCLC (28), HCC (31), CRC (32–34, 42), OC (36), CC (37) and osteosarcoma (43). These studies have elucidated its regulatory interactions with critical molecular targets, key signaling pathways, and essential biological processes that drive tumorigenesis and cancer progression, as illustrated in Figure 4 . LINC01123 functions as a pivotal oncogenic factor by regulating tumor cell proliferation, apoptosis, viability, invasion, migration, and EMT. Notably, LINC01123 is also implicated in stemness, glycolysis, angiogenesis, and resistance to various tumor therapies. These effects are mediated through diverse mechanisms, including the lncRNA-miRNA-mRNA ceRNA network, NOTCH and Hedgehog pathways, and interactions with SRSF7. Consequently, LINC01123 plays critical roles in tumor progression, glycolysis, tumor immunity, and therapy resistance. Targeting LINC01123 has thus emerged as a promising therapeutic strategy for cancer treatment.

Research on LINC01123 indicates its expression has been studied in nine types of solid tumors ( Table 1 ), including glioma (29), lung cancer (LUAD, NSCLC) (28, 30), OSCC (26), HNSCC (27), HCC (31), CRC (32–34), intrahepatic cholangiocarcinoma (35), OC (36) and CC (37), yet its presence in hematologic malignancies and other solid cancers remains unexplored. To establish its broader relevance, future studies should investigate its expression across hematologic malignancies and additional solid cancer types. Moreover, while LINC01123 has shown prognostic implications in seven tumor types (26–28, 31–33, 38), its clinical significance across diverse cancer stages and types requires validation through larger patient cohorts. On the other hand, LINC01123 has been implicated in various tumors, indicating a need for further in vivo and in vitro studies to delineate its specific roles and mechanisms in different cancer contexts. Its complex functions underscore the importance of gaining comprehensive insights into its involvement in distinct pathways and ceRNA networks, as well as lncRNA-protein interactions across different cancers. Additionally, studies have explored its potential associations with tumor metabolism in NSCLC (28) and immunity in HNSCC (27), while research into drug resistance is currently limited to radioresistance in glioma (29), chemotherapy resistance in LUAD (41), and colon cancer (34). Further studies are needed to explore these associations in more depth, mechanistically and across more cancer types.

In conclusion, LINC01123 has emerged as a newly identified and dysregulated cancer-associated lncRNA, highlighting its potential as both a promising biomarker and a key player in multiple critical aspects of tumor progression, metabolism, immune evasion, and therapeutic resistance. Targeting LINC01123 may offer new therapeutic avenues and enhance the efficacy of existing treatment options. However, further mechanistic investigations and large-scale comprehensive clinical studies are essential to elucidate its precise role in human cancer pathogenesis and to assess its clinical applicability.