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微小RNA MTCO3P38通过抑制TMOD1/MMP13通路减轻肝细胞癌进展

MicroRNA MTCO3P38 Inhibits the TMOD1/MMP13 Pathway to Alleviate the Progression of Hepatocellular Carcinoma.

作者信息

Wu Ping, Li Guoyuan, Guo Deliang, Guo Tao, Chai Chengwei

机构信息

Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, China.

Department of Hepatopancreatobiliary Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China.

出版信息

J Cancer. 2025 Jan 1;16(2):486-495. doi: 10.7150/jca.100556. eCollection 2025.

Abstract

Hepatocellular carcinoma (HCC) is one of the deadliest types of tumors. MicroRNA (miRNA) MTCO3P38 is a novel miRNA derived from the pseudogene MTCO3P38 with 18 nucleotides in length. The target genes of miR-MTCO3P38 were predicted by Targetscan, RNAhybrid and PITA. Transwell assays verified the effects of miR-MTCO3P38 and its target gene on the migration and invasion of HCC cells. , tumor growth was measured, and the impacts of miR-MTCO3P38 and its target gene on tumor pathology, proliferation, TMOD1/MMP13 pathway and tumor invasion-related factors were evaluated by hematoxylin-eosin staining, immunohistochemistry (Ki67) and western blot. , miR-MTCO3P38 could inhibit the migration and invasion of HCC cells. Mechanistically, miR-MTCO3P38 suppressed the expression of its target gene, tropomodulin 1 (TMOD1), by directly binding the 3'-untranslated region of TMOD1 and then inhibiting the MMP13 pathway. Tumor xenograft model mice were conducted, and assays further confirmed that miR-MTCO3P38 restrained tumor growth and proliferation in HCC by inhibiting the TMOD1/MMP13 pathway. MiR-MTCO3P38 suppresses the TMOD1/MMP13 pathway to alleviate HCC progression.

摘要

肝细胞癌(HCC)是最致命的肿瘤类型之一。微小RNA(miRNA)MTCO3P38是一种源自假基因MTCO3P38的新型miRNA,长度为18个核苷酸。通过Targetscan、RNAhybrid和PITA预测miR-MTCO3P38的靶基因。Transwell实验验证了miR-MTCO3P38及其靶基因对HCC细胞迁移和侵袭的影响。测量肿瘤生长情况,并通过苏木精-伊红染色、免疫组织化学(Ki67)和蛋白质印迹法评估miR-MTCO3P38及其靶基因对肿瘤病理学、增殖、TMOD1/MMP13通路和肿瘤侵袭相关因子的影响。miR-MTCO3P38可抑制HCC细胞的迁移和侵袭。机制上,miR-MTCO3P38通过直接结合TMOD1的3'-非翻译区来抑制其靶基因原肌球蛋白1(TMOD1)的表达,进而抑制MMP13通路。建立肿瘤异种移植模型小鼠,实验进一步证实miR-MTCO3P38通过抑制TMOD1/MMP13通路抑制HCC中的肿瘤生长和增殖。miR-MTCO3P38通过抑制TMOD1/MMP13通路来缓解HCC的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd40/11685701/94d345a5a9cd/jcav16p0486g001.jpg

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