:: Volume 9, Issue 4 (Int J Mol Cell Med 2020) ::
Int J Mol Cell Med 2020, 9(4): 273-287 Back to browse issues page
Downregulated Expression of WWOX in Cervical Carcinoma: A Case-Control Study
Shikha Srivastava1 , Uday Pratap Shahi2, Arti Divya3, Sadhana Gupta4 , Indu Singh5 , Jagat Kumar Roy 6
1- Cytogenetics Laboratory, Department of Zoology, Banaras Hindu University, Varanasi, India.
2- Department of Radiotherapy and Radiation Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
3- Indian Railways Cancer Institute and Research Centre, Varanasi, India.
4- Department of Obstetrics and Gynaecology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
5- Apollo Clinic, Mehmoorganj, Varanasi, India.
6- Cytogenetics Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University,Varanasi-221005, India. , jkroy@bhu.ac.in
Abstract:   (1027 Views)
Integration of human papilloma virus (HPV) in human genome is a random event, and fragile sites are one of the most susceptible sites for viral integrations. WWOX (WW-domain containing oxidoreductase) gene harbours the second most common fragile site, FRA16D, and can be an important candidate for HPV integration and cervical carcinogenesis. Our aim was to evaluate the potential role of WWOX in cervical carcinogenesis. Presence of HPV and its genotype was detected by PCR in normal cervix tissues and human cervical carcinoma. The expression of WWOX transcript and its protein was examined by RT-PCR, RNA in situ hybridization, and immunoblotting. Southern blotting and sequencing were used to determine the alternative transcripts of WWOX. Statistical analyses were performed by Mann Whitney U-test, Pearson correlation coefficient test at significance level of P value < 0.05. Prevalence of HPV was observed in cervicitis (40%), cervical intraepithelial neoplasia patients (50%), and invasive cervical carcinoma patients (89.6%). Clinicopathological findings suggested a correlation of reduced level of WWOX protein and progression of cervical carcinoma deciphering its role in tumorigenesis. Furthermore, we observed aberrant WWOX transcript having deleted exon 6-8 region in invasive cervical cancer tissues as well as normal cervix samples. More than 60% of cervical carcinoma samples showed reduced protein level with an increase in wild type transcript level suggesting the involvement of a negative regulator, pAck1 (activated Cdc42- associated kinase) which might ubiquitinate WWOX protein leading to its degradation. Also, nuclear retention of WWOX transcript in invasive cervical carcinoma tissues suggests its regulation at post-transcriptional level. Our findings suggest that WWOX acts as a tumor suppressor in cervical carcinoma and could act as a potential therapeutic target for the disease.
Keywords: Cervical cancer, clinical- pathological parameters, genotypes, cervical carcinoma patients, WWOX variants
Full-Text [PDF 735 kb]   (168 Downloads)    
Type of Study: Original Article | Subject: Cancer
Received: 2020/06/11 | Accepted: 2020/11/29 | Published: 2020/11/30

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Volume 9, Issue 4 (Int J Mol Cell Med 2020) Back to browse issues page