Investigating the effects of RBBP6 gene expression on telomerase activity in cervical cancer

Abstract

Cancer remains a major health problem. It is ranked the second most common cause of death to cardiovascular diseases worldwide, with about 9.6 million deaths annually. This burden is greatly carried by developing countries, which are accountable for about 65% of cancer death worldwide. Retinoblastoma binding protein 6 (RBBP6) is one of the genes identified as proliferative gene that plays a role in cancer development. It has been shown together with telomerase activity to be highly increased in various cancer cells. E6 protein of human papillomavirus (HPV) and RBBP6 are known to enhance the progression of cancer cells by interacting with p53 and presenting it for ubiquitination by the proteasome, thereby promoting cell proliferation and preventing apoptosis. Studies also show that HPV E6 protein has the ability to increase telomerase activity by activating the expression of human telomerase reverse transcriptase (hTERT) thus, enabling the immortalization of the cells. With RBBP6 and hTERT sharing similar functions, here we seek to investigate possible effect of RBBP6 expression on telomerase activity. Using real time qPCR and TRAPeze RT Telomerase detection kit (Merck, United states), CaSki cells showed that the expression of hTERT and telomerase activity, respectively, were decreased significantly in RBBP6-knockdown cells. However, HeLa cells showed non-significant changes in hTERT expression or telomerase activity in response to RBBP6 silencing. Real-time cell analysis assay revealed a significant cell growth reduction in cells co-silenced for RBBP6 and hTERT, thus substantiating our speculation that RBBP6 and hTERT play an additive role in cell proliferation. Taken all together, RBBP6 expression might be altering telomerase activity in a cell line dependent manner. RBBP6 and TERT co-silencing has an effect on cell proliferation.