Evidence map›Paper›PMID 42286554›Full record

ArticleBMC cancer2026

Methylation-mediated regulation of tumor-suppressor function of the miR-379/656 (C14MC) cluster and its clinical utility in hepatocellular carcinoma.

Shreyas Hulusemane Karunakara, Gopalakrishna Ramaswamy, Shama Prasada Kabekkodu, Akila Prashant, Prashant Vishwanath, Rohit Mehtani, Prasanna Kumar Santhekadur

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Article in BMC cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Shreyas Hulusemane KarunakaraCenter of Excellence in Molecular Biology and Regenerative Medicine, Department of Biochemistry, JSS Medical College and Hospital, Mysuru, India.ORCID http://orcid.org/0000-0002-1409-0823
Gopalakrishna RamaswamyTheracues Private Limited, Bengaluru, India.ORCID http://orcid.org/0009-0004-4643-4274
Shama Prasada KabekkoduDepartment of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India.ORCID http://orcid.org/0000-0002-4158-3893
Akila PrashantCenter of Excellence in Molecular Biology and Regenerative Medicine, Department of Biochemistry, JSS Medical College and Hospital, Mysuru, India.ORCID http://orcid.org/0000-0003-0383-2366
Prashant VishwanathCenter of Excellence in Molecular Biology and Regenerative Medicine, Department of Biochemistry, JSS Medical College and Hospital, Mysuru, India.ORCID http://orcid.org/0000-0003-1582-8057
Rohit MehtaniDepartment of Gastroenterology and Hepatology, BLK-Max Institute of Digestive and Liver disease, BLK-Max Super Speciality Hospital, New Delhi, India.ORCID http://orcid.org/0000-0002-0007-0063
Prasanna Kumar SanthekadurCenter of Excellence in Molecular Biology and Regenerative Medicine, Department of Biochemistry, JSS Medical College and Hospital, Mysuru, India. prasannakumars@jssuni.edu.in.ORCID http://orcid.org/0000-0003-3338-375X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHepatocellular carcinoma is a leading cause of cancer-related mortality. Several microRNAs play key roles in HCC development and progression. Epigenetic processes, such as DNA methylation, might regulate these RNAs during HCC pathogenesis. In this study, we show that the miR-379/656 cluster/C14MC acts as a tumor suppressor cluster and is epigenetically regulated by DNA methylation.

methodsC14MC miRNA expression was determined in HCC cell lines using the nCounter assay and from the TCGA-LIHC clinical cohort. C14MC putative promoter was identified, characterized using cloning and luciferase assay, and the methylation status of promoter-bound CpGs was determined using bisulfite Sanger sequencing. The expressions of C14MC targets were experimentally validated by transcriptomic sequencing or transfecting mimics, followed by qRT-PCR. Furthermore, the diagnostic and prognostic significance of C14MC and its target interactome in HCC was assessed using clinical data from the TCGA-LIHC cohort.

resultsC14MC was downregulated in HCC cell lines and in TCGA-LIHC. The loss of C14MC tumor suppressor function was directly regulated by the hypermethylation of promoter-CpGs. Reactivating specific C14MC miRNAs, such as miR-299-5p and miR-376c-3p via mimics, abrogated the expression of several target oncogenes, including PARP1, SPP1, RAD21, and CENPA, which regulate critical molecular pathways such as the p53 signaling and NF-κB signaling pathways in HCC. Additionally, overexpressing these miRNAs inhibited HCC cell migration and invasion. Also, C14MC and its target interactome exhibited significant clinical correlation in terms of survival outcomes of HCC patients.

conclusionsThis is the first study to show that C14MC is a methylation-dependent cluster in HCC. Several of these miRNAs and their targets can be used for early HCC diagnosis and prognosis. Thus, targeting C14MC can be useful in HCC management.

Indexed as

Carcinoma, HepatocellularDNA MethylationGene Expression Regulation, NeoplasticLiver NeoplasmsMicroRNAsCell Line, TumorCell MovementCell ProliferationCpG IslandsEpigenesis, GeneticGenes, Tumor SuppressorHumansPrognosisPromoter Regions, GeneticMicroRNAsMIRN376C microRNA, humanMIRN379 microRNA, humanC14MCDNA methylationHepatocellular carcinomamiR-379/656 clusterSurvival

Identifiers

PMID42286554
PMCPMC13488290

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.