miR-369-5p 通过下调 HOXA13 表达抑制肝癌细胞的增殖和迁移。
MiR-369-5p inhibits the proliferation and migration of hepatocellular carcinoma cells by down-regulating HOXA13 expression.
机构信息
Center of Hepatobiliary Pancreatic Disease, Beijing Tsinghua Changgung Hospital, China.
Department of Anesthesiology, Huashan Hospital, Fudan University, China.
出版信息
Tissue Cell. 2022 Feb;74:101721. doi: 10.1016/j.tice.2021.101721. Epub 2021 Dec 27.
MicroRNA (miRNA) is vital to the progression of hepatocellular carcinoma (HCC). Thereinto, miR-369-5p could yield assorted effects on various cancers, but there are few reports concerning the effect of miR-369-5p on HCC. Thus this study aimed to investigate the effect and mechanism of miR-369-5p in HCC. The data of miR-369-5p and HOXA13 expressions in liver hepatocellular carcinoma (LIHC) were analyzed by starBase, and then the miR-369-5p expression in HCC tissues and cells was detected by quantitative real-time PCR. Subsequently, miR-369-5p mimic was transfected into HCC cells and then its effects on cell activities were evaluated by cell counting kit-8, colony formation, wound healing, transwell assays, respectively. Expressions of epithelial-mesenchymal transition (EMT)-related genes were determined by western blot. The targeting relationship between miR-369-5p and HOXA13 was predicted by Targetscan and verified by dual-luciferase reporter assay. Pearson correlation test was used to analyze the correlation between HOXA13 and miR-369-5p. The above assays were experimented again to investigate the effects of HOXA13 on biological activity and EMT of HCC cells. MiR-369-5p expression was down-regulated and HOXA13 expression was up-regulated in LIHC. MiR-369-5p targeted HOXA13 and the expression of miR-369-5p was negatively correlated with the HOXA13 expression. MiR-369-5p inhibited the viability, proliferation, migration and invasion of HCC cells, increased E-cadherin level and decreased N-cadherin and Vimentin expressions. Concurrently, HOXA13 overexpression could counteract the effects of miR-369-5p on biological activity and EMT-related biomarkers of HCC cells. To conclude, miR-369-5p inhibits the viability, proliferation, migration and invasion of HCC cells by repressing the expression of HOXA13.
微小 RNA（miRNA）对肝细胞癌（HCC）的进展至关重要。其中，miR-369-5p 可能对各种癌症产生不同的影响，但关于 miR-369-5p 对 HCC 的影响的报道很少。因此，本研究旨在探讨 miR-369-5p 在 HCC 中的作用和机制。通过 starBase 分析 miR-369-5p 和 HOXA13 在肝肝细胞癌（LIHC）中的表达数据，然后通过定量实时 PCR 检测 HCC 组织和细胞中的 miR-369-5p 表达。随后，将 miR-369-5p 模拟物转染入 HCC 细胞中，然后通过细胞计数试剂盒-8、集落形成、划痕愈合、Transwell 测定分别评估其对细胞活性的影响。通过 Western blot 测定上皮-间充质转化（EMT）相关基因的表达。通过 Targetscan 预测 miR-369-5p 与 HOXA13 的靶向关系，并通过双荧光素酶报告基因测定验证。采用 Pearson 相关检验分析 HOXA13 与 miR-369-5p 的相关性。再次进行上述实验，以研究 HOXA13 对 HCC 细胞生物学活性和 EMT 的影响。在 LIHC 中，miR-369-5p 的表达下调，HOXA13 的表达上调。miR-369-5p 靶向 HOXA13，并且 miR-369-5p 的表达与 HOXA13 的表达呈负相关。miR-369-5p 抑制 HCC 细胞的活力、增殖、迁移和侵袭，增加 E-钙粘蛋白水平，降低 N-钙粘蛋白和波形蛋白的表达。同时，HOXA13 的过表达可以抵消 miR-369-5p 对 HCC 细胞生物学活性和 EMT 相关生物标志物的影响。总之，miR-369-5p 通过抑制 HOXA13 的表达抑制 HCC 细胞的活力、增殖、迁移和侵袭。
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