ArticleRadiation oncology (London, England)2012
Association of anti-apoptotic Mcl-1L isoform expression with radioresistance of oral squamous carcinoma cells.
Article in Radiation oncology (London, England), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- Dioscin suppresses tumorigenesis and overcomes radioresistance by promoting ubiquitination-mediated degradation of Mcl-1.Cancer gene therapy · 2026Article
- Application of Indirect ELISA and PCR Techniques for Detecting of Hepatocellular Carcinoma using Des-gamma Carboxyprothrombin, Alpha-fetoprotein, and Thioredoxin Biomarkers.Molecular biotechnology · 2026Article
- Targeting mitochondria as a potential therapeutic strategy against radioresistance in cancer.Frontiers in oncology · 2026Review
- Tipping the balance of cell death: alternative splicing as a source of MCL-1S in cancer.Cell death & disease · 2024Review
- Myeloid cell leukemia-1 expression in cancers of the oral cavity: a scoping review.Cancer cell international · 2022Article
- Myeloid cell leukemia-1: a formidable barrier to anticancer therapeutics and the quest of targeting it.Exploration of targeted anti-tumor therapy · 2022Review
- Emerging roles of alternative RNA splicing in oral squamous cell carcinoma.Frontiers in oncology · 2022Review
- Elevated USP9X drives early-to-late-stage oral tumorigenesis via stabilisation of anti-apoptotic MCL-1 protein and impacts outcome in oral cancers.British journal of cancer · 2021Article
- Identification of Candidate Target Genes and Immune Cells in Oral Squamous Cell Carcinoma.Computational and mathematical methods in medicine · 2021Article
- Article
- Function, clinical application, and strategies of Pre-mRNA splicing in cancer.Cell death and differentiation · 2019Review
- Divaricoside Exerts Antitumor Effects, in Part, by Modulating Mcl-1 in Human Oral Squamous Cell Carcinoma Cells.Computational and structural biotechnology journal · 2019Article
- Alternative-splicing defects in cancer: Splicing regulators and their downstream targets, guiding the way to novel cancer therapeutics.Wiley interdisciplinary reviews. RNA · 2018Review
- Article
- FTY720 Induces Autophagy-Associated Apoptosis in Human Oral Squamous Carcinoma Cells, in Part, through a Reactive Oxygen Species/Mcl-1-Dependent Mechanism.Scientific reports · 2017Article
- Oncoapoptotic markers in oral cancer: prognostics and therapeutic perspective.Molecular diagnosis & therapy · 2014Review
- Elevated SRPK1 lessens apoptosis in breast cancer cells through RBM4-regulated splicing events.RNA (New York, N.Y.) · 2014Article
- Radiation oncology in vitro: trends to improve radiotherapy through molecular targets.BioMed research international · 2014Review
- Overexpression of Mcl-1L splice variant is associated with poor prognosis and chemoresistance in oral cancers.PloS one · 2014Article
- Raman spectroscopic study of radioresistant oral cancer sublines established by fractionated ionizing radiation.PloS one · 2014Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOral cancer is a common cancer and a major health problem in the Indian subcontinent. At our laboratory Mcl-1, an anti-apoptotic member of the Bcl-2 family has been demonstrated to be overexpressed in oral cancers and to predict outcome in oral cancer patients treated with definitive radiotherapy. To study the role of Mcl-1 isoforms in radiation response of oral squamous carcinoma cells (OSCC), we investigated in the present study, the association of Mcl-1 isoform expression with radiosensitivity of OSCC, using siRNA strategy.
methodsThe time course expression of Mcl-1 splice variants (Mcl-1L, Mcl-1S & Mcl-1ES) was studied by RT-PCR, western blotting & immunofluorescence, post-irradiation in oral cell lines [immortalized FBM (radiosensitive) and tongue cancer AW8507 & AW13516 (radioresistant)]of relatively differing radiosensitivities. The effect of Mcl-1L knockdown alone or in combination with ionizing radiation (IR) on cell proliferation, apoptosis & clonogenic survival, was investigated in AW8507 & AW13516 cells. Further the expression of Mcl-1L protein was assessed in radioresistant sublines generated by fractionated ionizing radiation (FIR).
resultsThree to six fold higher expression of anti-apoptotic Mcl-1L versus pro-apoptotic Mcl-1S was observed at mRNA & protein levels in all cell lines, post-irradiation. Sustained high levels of Mcl-1L, downregulation of pro-apoptotic Bax & Bak and a significant (P < 0.05) reduction in apoptosis was observed in the more radioresistant AW8507, AW13516 versus FBM cells, post-IR. The ratios of anti to pro-apoptotic proteins were high in AW8507 as compared to FBM. Treatment with Mcl-1L siRNA alone or in combination with IR significantly (P < 0.01) increased apoptosis viz. 17.3% (IR), 25.3% (siRNA) and 46.3% (IR plus siRNA) and upregulated pro-apoptotic Bax levels in AW8507 cells. Combination of siRNA & IR treatment significantly (P < 0.05) reduced cell proliferation and clonogenic survival of radioresistant AW8507 & AW13516 cells, suggesting a synergistic effect of the Mcl-1L siRNA with IR on radiosensitivity. Interestingly, during the development of radioresistant sublines using FIR, high expression of Mcl-1L was observed.
conclusionOur studies suggest that Mcl-1L isoform has an important role in the survival and radioresistance of OSCC and may be a promising therapeutic target in oral cancers.
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