ArticlePloS one2014
Overexpression of Mcl-1L splice variant is associated with poor prognosis and chemoresistance in oral cancers.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 47 citations in OpenAlex.
- Dioscin suppresses tumorigenesis and overcomes radioresistance by promoting ubiquitination-mediated degradation of Mcl-1.Cancer gene therapy · 2026Article
- Alternative Splicing of Pre-mRNA Matters in Oral Diseases.Current gene therapy · 2025Review
- Tipping the balance of cell death: alternative splicing as a source of MCL-1S in cancer.Cell death & disease · 2024Review
- BRD-810 is a highly selective MCL1 inhibitor with optimized in vivo clearance and robust efficacy in solid and hematological tumor models.Nature cancer · 2024Article
- Expression of Truncated Products at the 5'-Terminal Region of RIPK2 and Evolutive Aspects that Support Their Biological Importance.Genome biology and evolution · 2024Article
- The interplay between non-coding RNAs and alternative splicing: from regulatory mechanism to therapeutic implications in cancer.Theranostics · 2023Review
- Decoding the concealed transcriptional signature of the apoptosis-related BCL2 antagonist/killer 1 (BAK1) gene in human malignancies.Apoptosis : an international journal on programmed cell death · 2022Article
- Myeloid cell leukemia-1 expression in cancers of the oral cavity: a scoping review.Cancer cell international · 2022Article
- Role of main RNA modifications in cancer: NSignal transduction and targeted therapy · 2022Review
- Emerging roles of alternative RNA splicing in oral squamous cell carcinoma.Frontiers in oncology · 2022Review
- Myeloid cell leukemia-1: a formidable barrier to anticancer therapeutics and the quest of targeting it.Exploration of targeted anti-tumor therapy · 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
- Antitumor Activity of the Cardiac Glycoside αlDiginoside by Modulating Mcl-1 in Human Oral Squamous Cell Carcinoma Cells.International journal of molecular sciences · 2020Article
- Exploring the potential of BH3 mimetic therapy in squamous cell carcinoma of the head and neck.Cell death & disease · 2019Article
- BCL-2 family isoforms in apoptosis and cancer.Cell death & disease · 2019Review
- Alternative-splicing defects in cancer: Splicing regulators and their downstream targets, guiding the way to novel cancer therapeutics.Wiley interdisciplinary reviews. RNA · 2018Review
- Myeloid cell leukemia 1 (MCL-1), an unexpected modulator of protein kinase signaling during invasion.Cell adhesion & migration · 2018Review
- Article
- Histone Deacetylase Inhibitor Enhances the Efficacy of MEK Inhibitor through NOXA-Mediated MCL1 Degradation in Triple-Negative and Inflammatory Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- 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
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAltered expression of Mcl-1, an anti-apoptotic member of the Bcl-2 family, has been linked to the progression and outcome of a variety of malignancies. We have previously reported the overexpression of Mcl-1 protein in human oral cancers. The present study aimed to evaluate the clinicopathological significance of the expression of three known Mcl-1 isoforms in oral tumors and the effect of targeting Mcl-1L isoform on chemosensitivity of oral cancer cells.
methodsThe expression of Mcl-1 isoforms- Mcl-1L, Mcl-1S & Mcl-1ES was analyzed in 130 paired oral tumors and 9 oral cell lines using quantitative real-time PCR & protein by western blotting. The Mcl-1 mRNA levels were correlated with clinicopathological parameters and outcome of oral cancer patients. The effect of Mcl-1L shRNA or Obatoclax (a small molecule Mcl-1 inhibitor), in combination with Cisplatin on chemosensitivity of oral cancer cells was also assessed.
resultsAnti-apoptotic Mcl-1L was predominantly expressed, over low or undetectable pro-apoptotic Mcl-1S and Mcl-1ES isoforms. The Mcl-1L transcripts were significantly overexpressed in all cancer cell lines and in 64% oral tumors versus adjacent normals (P<0.02). In oral cancer patients, high Mcl-1L expression was significantly associated with node positivity (P = 0.021), advanced tumor size (P = 0.013) and poor overall survival (P = 0.002). Multivariate analysis indicated Mcl-1L to be an independent prognostic factor for oral cancers (P = 0.037). Mcl-1L shRNA knockdown or its inhibition by Obatoclax in combination with Cisplatin synergistically reduced viability and growth of oral cancer cells than either treatment alone.
conclusionOur studies suggest that overexpression of Mcl-1L is associated with poor prognosis and chemoresistance in oral cancers. Mcl-1L is an independent prognostic factor and a potential therapeutic target in oral cancers.
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