幽门螺杆菌感染通过靶向 HOXA-AS2/miR-509-3p/MMD2 轴诱导胃癌细胞恶性转化。
Helicobacter pylori infection induces gastric cancer cell malignancy by targeting HOXA-AS2/miR-509-3p/MMD2 axis.
机构信息
Department of Gastroenterology, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, No. 228, Jingui Road, Xian'an District, Xianning, 437100, Hubei, China.
Department of Anus and Intestine Surgery, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, No. 228, Jingui Road, Xian'an District, Xianning, 437100, Hubei, China.
出版信息
Genes Genomics. 2024 Jun;46(6):647-657. doi: 10.1007/s13258-024-01500-2. Epub 2024 Apr 4.
BACKGROUND
Helicobacter pylori (Hp) infection is considered to be the strongest risk factor for gastric cancer (GC). Long non-coding RNA HOXA cluster antisense RNA 2 (HOXA-AS2) has been indicated to be significantly related to Hp infection in GC patients.
OBJECTIVE
To investigate the detailed role and molecular mechanism of lncRNA HOXA-AS2 in Hp-induced GC.
METHODS
GC cells were treated with Hp filtrate for cell infection. Bioinformatics tools were utilized for survival analysis and prediction of HOXA-AS2 downstream molecules. Western blotting and RT-qPCR were utilized for assessing protein and RNA levels, respectively. Flow cytometry, colony formation and CCK-8 assays were implemented for testing HOXA-AS2 functions in Hp-infected GC cells. HOXA-AS2 localization in cells was determined by subcellular fractionation assay. The relationship between RNAs were measured by luciferase reporter assay.
RESULTS
Hp infection induced HOXA-AS2 upregulation in GC cells. Knocking down HOXA-AS2 restrained cell proliferation but promoted cell apoptosis with Hp infection. HOXA-AS2 bound to miR-509-3p, and miR-509-3p targeted monocyte to macrophage differentiation associated 2 (MMD2). Overexpressing MMD2 reversed HOXA-AS2 depletion-mediated suppression on cell aggressiveness with Hp infection.
CONCLUSION
Hp infection induces the aggressiveness of GC cells by regulating HOXA-AS2/miR-509-3p/MMD2 axis.
背景
幽门螺杆菌（Hp）感染被认为是胃癌（GC）的最强危险因素。长链非编码 RNA HOXA 簇反义 RNA 2（HOXA-AS2）已被证明与 GC 患者的 Hp 感染显著相关。
目的
研究长链非编码 RNA HOXA-AS2 在 Hp 诱导的 GC 中的详细作用和分子机制。
方法
用 Hp 滤液处理 GC 细胞进行细胞感染。利用生物信息学工具进行生存分析和 HOXA-AS2 下游分子的预测。分别采用 Western blot 和 RT-qPCR 检测蛋白和 RNA 水平。流式细胞术、集落形成和 CCK-8 测定用于检测 Hp 感染 GC 细胞中 HOXA-AS2 的功能。通过亚细胞分级测定法确定细胞内 HOXA-AS2 的定位。通过荧光素酶报告测定法测量 RNA 之间的关系。
结果
Hp 感染诱导 GC 细胞中 HOXA-AS2 的上调。敲低 HOXA-AS2 可抑制细胞增殖，但在 Hp 感染时促进细胞凋亡。HOXA-AS2 与 miR-509-3p 结合，miR-509-3p 靶向单核细胞到巨噬细胞分化相关 2（MMD2）。过表达 MMD2 逆转了 HOXA-AS2 耗竭介导的 Hp 感染后细胞侵袭性的抑制。
结论
Hp 感染通过调节 HOXA-AS2/miR-509-3p/MMD2 轴诱导 GC 细胞的侵袭性。
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