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

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

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.

Keywords: MMP13; MTCO3P38; TMOD1; hepatocellular carcinoma; microRNA.