LINC00963: A potential cancer diagnostic and therapeutic target

Long intergenic noncoding RNA 00963 (LINC00963) is located on human chromosome 9q34.11. Aberrantly expressed LINC00963 often exerts oncogenic effects by regulating various cellular processes including proliferation, migration, invasion, EMT, and apoptosis. Overexpressed LINC00963 is associated with cancer clinicopathological features and poor cancer prognosis, and can be used in the diagnosis of hepatocellular carcinoma. LINC00963 can build a complex ceRNA network by competitively binding to 22 miRNAs in 14 cancers. LINC00963 can also directly regulate four downstream protein-coding genes. Specifically, LINC00963 promotes the transition of prostate cancer from an androgen-dependent mode to an androgen-independent mode by participating in the transactivation of EGFR. LINC00963 can bind EZH2 and inhibit p21 expression, thereby promoting glioma cell proliferation and invasion. In non-small cell lung cancer, LINC00963 can recruit NONO and CRTC, forming a positive feedback loop of LINC00963/NONO/CRTC/CREB/LINC00963, thereby promoting cancer cell metastasis. LINC00963 is involved in the PI3K/AKT signaling pathway, Wnt signaling pathway, AMPK signaling pathway, and MAPK signaling pathway. Furthermore, LINC00963 is associated with drug resistance in oral squamous cell carcinoma (cisplatin and 5-fluorouracil) and gastric cancer (oxaliplatin) and predicts neoadjuvant efficacy of taxane-anthracyclines in breast cancer. This work systematically reviewed the clinical value of abnormal expression of LINC00963 in various tumors, demonstrated the complex molecular mechanism of LINC00963, and provided directions for future related research.