Zhu Hong, Tang Jin-Hai, Zhang Shi-Meng, Qian Jia-Ping, Ling Xin, Wu Xiao-Ying, Yang Ling-Xia
Department of Gastroenterology, Suzhou Ninth People's Hospital, Suzhou, Jiangsu Province, People's Republic of China.
Onco Targets Ther. 2020 Dec 22;13:12999-13013. doi: 10.2147/OTT.S274708. eCollection 2020.
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.
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.
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.
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.
胃癌（GC）是一种在全球范围内发病率和死亡率都很高的常见癌症。近年来，越来越多的证据表明，长链非编码RNA（lncRNAs）通过作为肿瘤启动子或抑制剂在癌症的发生和发展中发挥关键作用。LINC00963是一种新报道的与癌症相关的lncRNA，其在胃癌中的作用仍不清楚。
使用定量实时PCR或蛋白质免疫印迹法检测LINC00963、miR-612和细胞分裂周期5样蛋白（CDC5L）的表达水平。通过Transwell和增殖实验分析LINC00963、miR-612和CDC5L在胃癌细胞中的生物学功能。使用Oncomine数据库评估胃癌患者中CDC5L的表达。骨髓来源的树突状细胞（DCs）取自C57BL/6小鼠。
LINC00963在胃癌组织中的表达高于相邻正常组织。在胃癌细胞系和正常人胃上皮细胞中也发现了类似的结果。LINC00963的上调与胃癌患者的不良预后相关。敲低LINC00963可抑制胃癌细胞的增殖、侵袭和转移，但促进其凋亡。此外，在胃癌细胞中沉默LINC00963可显著抑制胃癌的肿瘤生长。生物信息学分析表明，LINC00963可作为竞争性内源性RNA靶向miR-612。miR-612在胃癌组织和细胞系中的表达降低。同时，LINC00963的表达与miR-612呈负相关。CDC5L是miR-612的直接靶点。miR-612抑制胃癌组织和细胞中CDC5L的表达。此外，LINC00963通过调节DCs中miR-612的表达抑制DCs的分化和成熟。
LINC00963通过竞争性结合miR-612来调节CDC5L的表达，促进胃癌的进展，并介导与DC相关的抗肿瘤免疫反应。因此，靶向LINC00963可能是一种有前景的胃癌治疗策略。
