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

IF 3.3 3区 医学 Q2 ONCOLOGY Journal of Cancer Pub Date : 2025-01-01 DOI:10.7150/jca.100556
Ping Wu, Guoyuan Li, Deliang Guo, Tao Guo, Chengwei Chai
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Abstract

Background: 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. Methods: 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. In vivo, 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. Results: In vitro, 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 in vivo assays further confirmed that miR-MTCO3P38 restrained tumor growth and proliferation in HCC by inhibiting the TMOD1/MMP13 pathway. Conclusion: MiR-MTCO3P38 suppresses the TMOD1/MMP13 pathway to alleviate HCC progression.

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MicroRNA MTCO3P38抑制TMOD1/MMP13通路缓解肝细胞癌进展
背景:肝细胞癌(HCC)是最致命的肿瘤之一。MicroRNA (miRNA) MTCO3P38是由假基因MTCO3P38衍生而来的一种新型miRNA,长度为18个核苷酸。方法:采用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。在体内检测肿瘤生长,通过苏木精-伊红染色、免疫组织化学(Ki67)和western blot检测miR-MTCO3P38及其靶基因对肿瘤病理、增殖、TMOD1/MMP13通路和肿瘤侵袭相关因素的影响。结果:在体外,miR-MTCO3P38能够抑制HCC细胞的迁移和侵袭。在机制上,miR-MTCO3P38通过直接结合TMOD1的3'-非翻译区,进而抑制MMP13通路,从而抑制其靶基因原调节蛋白1 (troomodulin 1, TMOD1)的表达。建立肿瘤异种移植模型小鼠,体内实验进一步证实miR-MTCO3P38通过抑制TMOD1/MMP13通路抑制HCC中肿瘤的生长和增殖。结论:MiR-MTCO3P38抑制TMOD1/MMP13通路缓解HCC进展。
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来源期刊
Journal of Cancer
Journal of Cancer ONCOLOGY-
CiteScore
8.10
自引率
2.60%
发文量
333
审稿时长
12 weeks
期刊介绍: Journal of Cancer is an open access, peer-reviewed journal with broad scope covering all areas of cancer research, especially novel concepts, new methods, new regimens, new therapeutic agents, and alternative approaches for early detection and intervention of cancer. The Journal is supported by an international editorial board consisting of a distinguished team of cancer researchers. Journal of Cancer aims at rapid publication of high quality results in cancer research while maintaining rigorous peer-review process.
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