Liu Junzheng, Wang Lei, Li Jie, Xu Yu
Digestive System Department, Cangzhou People`s Hospital, Cangzhou, China.
Department of General Surgery, Eastern Hospital of the Second Hospital of Hebei Medical University, Shijiazhuang, China.
Neoplasma. 2021 Mar;68(2):262-272. doi: 10.4149/neo_2020_200806N823. Epub 2020 Nov 5.
Helicobacter pylori (HP) infection induces the development of gastric carcinoma (GC), one of the most frequent and fatal cancers worldwide, via a progressive cascade. The roles of microRNAs (miRNAs) involved in the cascade and the behind mechanisms, however, are still unclear. This study was designed to investigate the expression of miR-650, a well-recognized oncogenic miRNA in GC samples and to analyze the associations between this miRNA and HP infection, and the molecular mechanism. Following miRNA- and mRNA-based microarray analyses, miR-650, pre-B-cell leukemia transcription factor 1 (PBX1), and LATS2 were filtered as targets. After that, function assays were implemented to assess their function in GC cells. miR-650 was upregulated in HP+ tissues and cells, and inhibition of miR-650 attenuated cell proliferation, invasion, migration, yet enhanced apoptosis. PBX1 was overexpressed in HP+ tissues and cells and promoted miR-650 transcription. Overexpression of PBX1 abrogated the effect of the miR-650 inhibitor on GC cells. miR-650 targeted LATS2, and LATS2 was poorly expressed in HP+ tissues and cell lines. Simultaneous knockdown of miR-650 and LATS2 reduced GC cell apoptosis. These results display that upregulation of miR-650 induced by HP infection and PBX1 dampens LATS2 in GC cells, potentially offering novel intervention targets for GC.
幽门螺杆菌（HP）感染通过一个渐进的级联反应诱发胃癌（GC），胃癌是全球最常见且致命的癌症之一。然而，参与该级联反应的微小RNA（miRNA）的作用及其潜在机制仍不清楚。本研究旨在调查miR-650（一种在GC样本中公认的致癌miRNA）的表达情况，并分析该miRNA与HP感染之间的关联及其分子机制。基于miRNA和mRNA的微阵列分析后，筛选出miR-650、前B细胞白血病转录因子1（PBX1）和大肿瘤抑制激酶2（LATS2）作为靶点。之后，进行功能测定以评估它们在GC细胞中的功能。miR-650在HP阳性组织和细胞中上调，抑制miR-650可减弱细胞增殖、侵袭和迁移，但增强细胞凋亡。PBX1在HP阳性组织和细胞中过表达，并促进miR-650转录。PBX1的过表达消除了miR-650抑制剂对GC细胞的作用。miR-650靶向LATS2，且LATS2在HP阳性组织和细胞系中表达较低。同时敲低miR-650和LATS2可减少GC细胞凋亡。这些结果表明，HP感染和PBX1诱导的miR-650上调会抑制GC细胞中的LATS2，这可能为GC提供新的干预靶点。
