Wang Ping, Guan Qunye, Zhou Dongmei, Yu Ze, Song Yaobo, Qiu Wensheng
1 Department of Oncology, Yantaishan Hospital , Yantai, China .
2 Department of Gastroenterology, Weihai Municipal Hospital , Weihai, China .
DNA Cell Biol. 2018 Jan;37(1):38-45. doi: 10.1089/dna.2017.3922. Epub 2017 Nov 29.
Gastric cancer is one of the most common malignancy in the world. microRNAs (miRNAs) are naturally occurring noncoding RNA that control gene expression by targeting messenger RNA (mRNA) for post-transcriptional repression or cleavage. This study focused on a specific miRNA, miR-21, which was overexpressed in gastric cancer and examined the effects of miR-21 inhibitor on biological functions of gastric cancer cells and its possible mechanism. Gastric cancer cells MKN74 were treated with miR-21 inhibitor, negative control, and blank control. Cell proliferation, colony formation, migration, and invasion were assessed. Real-time PCR and western blot were applied to examine the expression of phosphatase and tens in homolog deleted on chromosome ten (PTEN)/PI3K/mTOR pathway molecules. miR-21 inhibitor markedly suppressed proliferation, migration, invasion, and colony formation of gastric cancer cells. Anti-miR-21 treatment also reduced the expression ratio of B cell lymphoma 2 (Bcl-2)/Bax. Furthermore, miR-21 inhibition was associated with increased expression of PTEN, which in turn decreased the ratios of S235/236, S240/244, and p-AK/AKT in gastric cancer cells. Inhibiting miR-21 modulates biological functions of gastric cancer cells via PTEN/PI3K/mTOR pathway and miR-21 inhibitor may provide a novel therapeutic strategy for gastric cancer.
胃癌是世界上最常见的恶性肿瘤之一。微小RNA(miRNA)是天然存在的非编码RNA,通过靶向信使RNA(mRNA)进行转录后抑制或切割来控制基因表达。本研究聚焦于一种在胃癌中过表达的特定miRNA,即miR-21,并研究了miR-21抑制剂对胃癌细胞生物学功能的影响及其可能机制。用miR-21抑制剂、阴性对照和空白对照处理胃癌细胞MKN74。评估细胞增殖、集落形成、迁移和侵袭情况。应用实时聚合酶链反应(PCR)和蛋白质免疫印迹法检测第10号染色体缺失的磷酸酶和张力蛋白同源物(PTEN)/磷脂酰肌醇-3激酶(PI3K)/哺乳动物雷帕霉素靶蛋白(mTOR)通路分子的表达。miR-21抑制剂显著抑制胃癌细胞的增殖、迁移、侵袭和集落形成。抗miR-21处理还降低了B细胞淋巴瘤-2(Bcl-2)/Bax的表达比值。此外,抑制miR-21与PTEN表达增加有关,这反过来又降低了胃癌细胞中S235/236、S240/244和磷酸化AKT(p-AK)/AKT的比值。抑制miR-21通过PTEN/PI3K/mTOR通路调节胃癌细胞的生物学功能,miR-21抑制剂可能为胃癌提供一种新的治疗策略。