Downregulated Expression of WWOX in Cervical Carcinoma: A Case-Control Study.

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. (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 in cervical carcinogenesis. Presence of HPV and its genotype was detected by PCR in normal cervix tissues and human cervical carcinoma. The expression of transcript and its protein was examined by RT-PCR, RNA hybridization, and immunoblotting. Southern blotting and sequencing were used to determine the alternative transcripts of . Statistical analysis 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 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 transcript in invasive cervical carcinoma tissues suggests its regulation at post-transcriptional level. Our findings suggest that acts as a tumor suppressor in cervical carcinoma and could act as a potential therapeutic target for the disease.