Sumedha Guha, Techno India University
Uncontrolled cell growth and division unleashed by an alteration (known as ‘mutation’) in the genetic circuits that regulate the cell cycle in a normal cell lead to cancer. In women, cervical cancer is the 2nd most commonly occurring cancer with more than 500,000 cases reported worldwide and 200,000 deaths. Cervical cancer alone accounts for 12% of all cancers that affect women.
Clinical studies have shown that in 90% of cervical cancer patients an incidence of Human Papilloma Virus (HPV) infection has been found. Following that, scientists have taken the help of HPV screening and HPV vaccination to significantly reduce HPV infection which consequently leads to a decreased incidence of cervical cancer. But even after bringing that under control, HPV negative cervical cancer has shown an increasing trend in recent years.
Apart from HPV infection, genetic factors play a huge role in the development and progression of cervical cancers. Analysis of the human transcriptome has revealed that 98% of transcripts are related to non-coding RNAs or ncRNAs. Long ncRNAs (>200 nt) involved in physiological and various pathological processes regulate the expression of oncogenic or tumour-suppressive genes to promote or inhibit cancer development. Therefore, the role of lncRNA expression has been found to be substantial in assisting cancer prevention and treatment.
Even though the role of most lncRNAs remains unclear, the role of GATA6-AS has been investigated and has given promising results. LncRNA GATA6-AS inhibits cancer cell proliferation and promotes cancer cell apoptosis. It regulates endothelial cell growth and also downregulates expression of miR-205, the over-expression of which is indicative of Cervical Squamous Cell Carcinoma (CSCC). It does so by epigenetically regulating gene expression.
A study was carried out on the plasma of 65 cervical squamous cell carcinoma (CSCC) patients and 58 healthy females to investigate the involvement of GATA6-AS in CSCC, a major subtype of cervical cancers, and to explore its possible interaction with miR-205. Preliminary microarray data revealed that the expression of plasma GATA6-AS is down-regulated in cervical cancer, and its expression inversely correlated with miR-205 expression. In addition, ROC curve analysis showed that downregulation of GATA6-AS expression distinguished CSCC patients from healthy patients. This indicates the use of plasma GATA6-AS levels as a promising diagnostic marker in cervical squamous cell carcinoma patients.
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