ArticleThe Journal of biological chemistry2012
DNA methylation-regulated miR-193a-3p dictates resistance of hepatocellular carcinoma to 5-fluorouracil via repression of SRSF2 expression.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 108 citations in OpenAlex.
- Crosstalk between alternative splicing and non-coding RNAs in hepatocellular carcinoma: from regulatory mechanism to therapeutic implications.Non-coding RNA research · 2026Review
- Multidimensional regulatory roles and therapeutic applications of SRSF7 in cancer.Cell death discovery · 2025Review
- Targeting microRNA methylation: Innovative approaches to diagnosing and treating hepatocellular carcinoma.Non-coding RNA research · 2025Review
- RNA splicing: a dual-edged sword for hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2022Review
- Review
- Mig-6 Inhibits Autophagy in HCC Cell Lines by Modulating miR-193a-3p.International journal of medical sciences · 2022Article
- A New Functional Gene, Zinc Finger Protein 485 (ZNF485), is Involved in Bladder Cancer Proliferation.Bladder cancer (Amsterdam, Netherlands) · 2022Article
- The Role of miRNA in the Pathophysiology of Neuroendocrine Tumors.International journal of molecular sciences · 2021Review
- Transcriptome-wide analysis reveals insight into tumor suppressor functions of 1B3, a novel synthetic miR-193a-3p mimic.Molecular therapy. Nucleic acids · 2021Article
- The DNA methylation-regulated MCTP1 activates the drug-resistance of esophageal cancer cells.Aging · 2021Article
- SPNS2 Downregulation Induces EMT and Promotes Colorectal Cancer MetastasisFrontiers in oncology · 2021Article
- Splicing factor SRSF2-centric gene regulation.International journal of biological sciences · 2021Review
- 5-Fluorouracil: A Narrative Review on the Role of Regulatory Mechanisms in Driving Resistance to This Chemotherapeutic Agent.Frontiers in oncology · 2021Review
- Non-Coding RNAs: Regulating Disease Progression and Therapy Resistance in Hepatocellular Carcinoma.Cancers · 2020Review
- Restoration of miR-193a expression is tumor-suppressive in MYC amplified Group 3 medulloblastoma.Acta neuropathologica communications · 2020Article
- Identification of a 3,3-difluorinated tetrahydropyridinol compound as a novel antitumor agent for hepatocellular carcinoma acting via cell cycle arrest through disturbing CDK7-mediated phosphorylation of Cdc2.Investigational new drugs · 2020Article
- LncRNA UCA1 Affects the Cell Proliferation, Migration, Invasion and Apoptosis of Hepatic Carcinoma Cells by Targeting MicroRNA-193a-3p.Cancer management and research · 2020Article
- Hsa_circ_0006916 Knockdown Represses the Development of Hepatocellular Carcinoma via Modulating miR-599/SRSF2 Axis.OncoTargets and therapy · 2020Article
- Alternative Splicing in Hepatocellular Carcinoma.Cellular and molecular gastroenterology and hepatology · 2020Review
- Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemoresistance prevents effective cancer therapy and is rarely predictable prior to treatment, particularly for hepatocellular carcinoma (HCC). Following the chemoresistance profiling of eight HCC cell lines to each of nine chemotherapeutics, two cell lines (QGY-7703 as a sensitive and SMMC-7721 as a resistant cell line to 5-fluorouracil (5-FU) treatment) were systematically studied for mechanistic insights underpinning HCC 5-FU chemoresistance. Genomic profiling at both DNA methylation and microRNA (miR) levels and subsequent mechanistic studies illustrate a new mechanism for how DNA methylation-regulated miR-193a-3p dictates the 5-FU resistance of HCC cells via repression of serine/arginine-rich splicing factor 2 (SRSF2) expression. In turn, SRSF2 preferentially up-regulates the proapoptotic splicing form of caspase 2 (CASP2L) and sensitizes HCC cells to 5-FU. Forced changes of miR-193a-3p level reverse all of the phenotypic features examined, including cell proliferation, cell cycle progression, and 5-FU sensitivity, in cell culture and in nude mice. Importantly, the siRNA-mediated repression of SRSF2 phenocopies all of the miR-193a-3p mimic-triggered changes in QGY-7703. This newly identified miR-193a-3p-SRSF2 axis highlights a new set of companion diagnostics required for optimal 5-FU therapy of HCC, which involve assaying both the DNA methylation state of the miR-193a gene and the expression of miR-193a-3p and SRSF2 and the relative level of the proapoptotic versus antiapoptotic splicing forms of caspase 2 in clinical samples.
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Registered trials
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.