Inhibition of BIRC2 Sensitizes α7-HPV-Related Cervical Squamous Cell Carcinoma to Chemotherapy.
Chiao-Yun LinChun-Chieh WangRen-Chin WuLan-Yan YangChen-Bin ChangYu-Bin PanAngel ChaoChyong-Huey LaiPublished in: International journal of molecular sciences (2021)
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.
Keyphrases
- poor prognosis
- squamous cell carcinoma
- long non coding rna
- locally advanced
- high grade
- free survival
- cell proliferation
- endothelial cells
- high resolution
- prognostic factors
- radiation therapy
- rectal cancer
- oxidative stress
- high throughput
- cervical cancer screening
- cell death
- metabolic syndrome
- mass spectrometry
- adipose tissue
- drug induced
- lymph node metastasis
- dna methylation
- drug delivery
- induced apoptosis
- long noncoding rna
- newly diagnosed
- glycemic control