Background: Gastric cancer (GC) is a common cancer with high incidence and mortality worldwide. In recent years, accumulating evidence has shown that long noncoding RNAs (lncRNAs) exert critical roles in the development and progression of cancer by acting as a tumor initiator or suppressor. LINC00963 is a newly reported lncRNA related to cancer, and its role in GC remains unclear.
Materials and Methods: The expression levels of LINC00963, miR-612, and cell division cycle 5-like protein (CDC5L) were measured using quantitative real-time PCR or Western blot. The biological functions of LINC00963, miR-612, and CDC5L in GC cells were analyzed by transwell and proliferation experiments. The expression of CDC5L in patients with GC was evaluated using the Oncomine database. Bone marrow-derived dendritic cells (DCs) were derived from C57BL/6 mice.
Results: LINC00963 expression was higher in GC tissues than in adjacent normal tissues. Similar results were found in GC cell lines and normal human gastric epithelial cells. Upregulation of LINC00963 was related to the poor prognosis of patients with GC. Knockdown of LINC00963 inhibited the proliferation, invasion, and metastasis but promoted the apoptosis of GC cells. Furthermore, silencing of LINC00963 in GC cells significantly suppressed the tumor growth of GC. Bioinformatics analysis indicated that LINC00963 could target miR-612 by functioning as a competing endogenous RNA. The expression of miR-612 decreased in GC tissues and cell lines. Meanwhile, LINC00963 expression was negatively associated with miR-612. CDC5L was a direct target of miR-612. miR-612 suppressed the expression of CDC5L in GC tissues and cells. Moreover, LINC00963 inhibited the differentiation and maturation of DCs by regulating miR-612 expression in DCs.
Conclusion: LINC00963 promoted the progression of GC by competitively binding to miR-612 to regulate the expression of CDC5L and mediated DC-related anti-tumor immune response. Thus, targeting LINC00963 may be a promising therapeutic strategy for GC.
Keywords: lncRNA LINC00963, gastric cancer, miR-612, CDC5L, dendritic cells