A pinboard by
Gbemisola Saibu

Senior Lecturer, Lagos State University


Genes implicated in Cervical Cancer

Cancer is a global burden, with the increasing incidence of the various forms of cancers such as cervical cancers especially in the developing world such as Nigeria, cancer patients continue to explore alternative treatments, therefore, the need for reliable scientific data and extensive research with potentials for more effective and efficacious cancer prevention and treatment cannot be overemphasized. My research focus has been to promote and undertake cancer based researches with potentials to achieve the aforementioned. My research interest is broadly categorised as follows:

  1. Basic research: aims to explore the mechanism and the molecular basis of cancer with a view to enhancing an understanding of how cancer develops and also provide the foundation for developing potential chemo prophylactic or therapeutic agents or diagnostic tests for cancers.
  2. Translational research (drug discovery and development): aims to utilize the knowledge gained from basic research or the understanding of cancer biology to develop potential new treatments or diagnostic tests for various cancers.
  3. Population and Behavioral research (Epidemiological research): aims to determine the burden of the various forms of cancers in Nigeria, identify the risks for cancers, and also look at how our behavior or lifestyles can predispose to or protect against cancers.
  4. Research on Dietary influence in Cancer: aims to determine the dietary pattern of Cancer patients and survivors in other to investigate the bioactive components of foods that could be beneficial to cancer patients.

Inactivation of the human papillomavirus E6 or E7 gene in cervical carcinoma cells by using a bacterial CRISPR/Cas RNA-guided endonuclease.

Abstract: High-risk human papillomaviruses (HPVs), including HPV-16 and HPV-18, are the causative agents of cervical carcinomas and are linked to several other tumors of the anogenital and oropharyngeal regions. The majority of HPV-induced tumors contain integrated copies of the normally episomal HPV genome that invariably retain intact forms of the two HPV oncogenes E6 and E7. E6 induces degradation of the cellular tumor suppressor p53, while E7 destabilizes the retinoblastoma (Rb) protein. Previous work has shown that loss of E6 function in cervical cancer cells induces p53 expression as well as downstream effectors that induce apoptosis and cell cycle arrest. Similarly, loss of E7 allows increased Rb expression, leading to cell cycle arrest and senescence. Here, we demonstrate that expression of a bacterial Cas9 RNA-guided endonuclease, together with single guide RNAs (sgRNAs) specific for E6 or E7, is able to induce cleavage of the HPV genome, resulting in the introduction of inactivating deletion and insertion mutations into the E6 or E7 gene. This results in the induction of p53 or Rb, leading to cell cycle arrest and eventual cell death. Both HPV-16- and HPV-18-transformed cells were found to be responsive to targeted HPV genome-specific DNA cleavage. These data provide a proof of principle for the idea that vector-delivered Cas9/sgRNA combinations could represent effective treatment modalities for HPV-induced cancers. Importance: Human papillomaviruses (HPVs) are the causative agents of almost all cervical carcinomas and many other tumors, including many head and neck cancers. In these cancer cells, the HPV DNA genome is integrated into the cellular genome, where it expresses high levels of two viral oncogenes, called E6 and E7, that are required for cancer cell growth and viability. Here, we demonstrate that the recently described bacterial CRISPR/Cas RNA-guided endonuclease can be reprogrammed to target and destroy the E6 or E7 gene in cervical carcinoma cells transformed by HPV, resulting in cell cycle arrest, leading to cancer cell death. We propose that viral vectors designed to deliver E6- and/or E7-specific CRISPR/Cas to tumor cells could represent a novel and highly effective tool to treat and eliminate HPV-induced cancers.

Pub.: 08 Aug '14, Pinned: 04 Sep '17