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Inhibition of BIRC2 Sensitizes α7-HPV-Related Cervical Squamous Cell Carcinoma to Chemotherapy.
- Source :
- International Journal of Molecular Sciences; Oct2021, Vol. 22 Issue 20, p11020, 1p
- Publication Year :
- 2021
-
Abstract
- The α7-human papillomavirus (HPV)-related cervical squamous cell carcinoma (SCC) is associated with poor prognosis. We compared the genomic profiles of this disease in a cohort corresponding to the 2001–2014 period with various responses to radiotherapy or concurrent chemoradiation through microRNA (miR) profiling involving miR 4.0 array and human transcriptome array 2.0 analyses. A real-time quantitative polymerase chain reaction was then conducted to identify the predictive biomarkers. A significantly lower expression of miR143-3p in recurrent tumors (p = 0.0309) relative to that in nonrecurrent tumors was observed. The miR143-3p targeted the mRNA expression of the baculoviral inhibitor of the apoptosis protein (IAP) repeat-containing 2 (BIRC2; p = 0.0261). The BIRC2 protein levels (p = 0.0023) were significantly higher in recurrent tumors than in nonrecurrent tumors. Moreover, the miR-143-3p sensitized the response of α7-HPV-related cervical SCC to chemotherapy by targeting BIRC2. A combination of BIRC2-inhibitor LCL161 and topotecan exerted synergistic effects on cancer cells and animal tumor models. In a pooled cohort of α7-HPV-related cervical SCC (including mixed infections with non-α7-HPV) treated between 1993 and 2014, high BIRC2 expression was associated with significantly worse outcomes (cancer-specific survival, hazard ratio (HR) = 1.42, p = 0.008; progression-free survival, HR = 1.64; p = 0.005). Summarily, BIRC2 constitutes a novel prognostic factor and therapeutic target for α7-HPV-related cervical SCC. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 16616596
- Volume :
- 22
- Issue :
- 20
- Database :
- Complementary Index
- Journal :
- International Journal of Molecular Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 153289092
- Full Text :
- https://doi.org/10.3390/ijms222011020