PMID- 35400271 OWN - NLM STAT- MEDLINE DCOM- 20220412 LR - 20220716 IS - 2165-5987 (Electronic) IS - 2165-5979 (Print) IS - 2165-5979 (Linking) VI - 13 IP - 4 DP - 2022 Apr TI - CircSEC24A (hsa_circ_0003528) interference suppresses epithelial-mesenchymal transition of hepatocellular carcinoma cells via miR-421/MMP3 axis. PG - 9049-9062 LID - 10.1080/21655979.2022.2057761 [doi] AB - Accumulating evidence indicates that circular RNAs (circRNAs) function as conclusive modulators in diverse tumors, including in hepatocellular carcinoma (HCC). Nonetheless, knowledge of the latent mechanisms involving circRNAs in HCC development is insufficient. circSEC24A (hsa_circ_0003528) was discovered by microarray analysis of patients with HCC. Binding sites between circSEC24A, miR-421, miR-421 and matrix metalloproteinase 3 (MMP3) were predicted using online bioinformatics tools. Interactions involving miRNA and target genes or circRNAs were verified by luciferase reporter-gene and RNA pull-down assays. Two HCC cell lines (HCCLM3 and Hep3B) and normal THLE-2 liver cells were used for in vitro experiments. miRNA and mRNA expression levels were detected by RT-qPCR, and protein expression was measured by western blotting. Cell proliferation was evaluated using Cell Counting Kit 8 (CCK-8) assays along with colony formation assays. Cell invasion and migration were determined using the Transwell and wound healing migration assays. A xenograft model was used to evaluate the role of circSEC24A in vivo. circSEC24A expression was significantly upregulated in HCCLM3 and Hep3B cells. Silencing circSEC24A mitigated the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of HCC cells, which was abrogated by downregulation of miR-421. Meanwhile, MMP3 could bind to miR-421 to decrease the functional effects of miR-421 and induce tumor metastasis. Knockdown of cicSEC24A suppressed tumor growth in vivo. circSEC24A interference suppressed HCC cell EMT by sponging miR-421, further regulating MMP3, and inhibiting tumor growth in vivo. Therefore, circSEC24A could represent a potential target for HCC patient treatment. FAU - Zhang, Bo AU - Zhang B AD - Department of Basic Medicine, Chongqing Medical and Pharmaceutical College, Chongqing, China. FAU - Zhou, Jian AU - Zhou J AD - Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China. AD - Department of Pathology, the First Affiliated Hospital of ChengDu Medical College, Chengdu, Sichuan, China. LA - eng PT - Journal Article PL - United States TA - Bioengineered JT - Bioengineered JID - 101581063 RN - 0 (MIRN421 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Circular) RN - EC 3.4.24.17 (MMP3 protein, human) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - *Carcinoma, Hepatocellular/metabolism MH - Cell Line, Tumor MH - Cell Proliferation/genetics MH - Epithelial-Mesenchymal Transition/genetics MH - Gene Expression Regulation, Neoplastic/genetics MH - Humans MH - *Liver Neoplasms/metabolism MH - Matrix Metalloproteinase 3/genetics/metabolism MH - *MicroRNAs/genetics/metabolism MH - RNA, Circular/genetics PMC - PMC9161912 OTO - NOTNLM OT - MMP3 OT - circSEC24A OT - competing endogenous RNA OT - hepatocellular carcinoma (HCC) OT - hsa_circ_0003528 OT - miR-421 COIS- No potential conflict of interest was reported by the author(s). EDAT- 2022/04/12 06:00 MHDA- 2022/04/13 06:00 PMCR- 2022/04/10 CRDT- 2022/04/11 05:23 PHST- 2022/04/11 05:23 [entrez] PHST- 2022/04/12 06:00 [pubmed] PHST- 2022/04/13 06:00 [medline] PHST- 2022/04/10 00:00 [pmc-release] AID - 2057761 [pii] AID - 10.1080/21655979.2022.2057761 [doi] PST - ppublish SO - Bioengineered. 2022 Apr;13(4):9049-9062. doi: 10.1080/21655979.2022.2057761.