Identification of Therapeutic Targets and Suitable Compounds for the Treatment of Colorectal Cancer by using High Throughput Sequencing and Virtual Screening

Abstract

Colorectal cancer (CRC) is an abnormal growth in the lining of the colon and rectum. The early abnormal growth of CRC is called precancerous Polyps. If left untreated the uncontrolled growth turns into mature Polyps. The most common type of CRC is adenocarcinomas which usually occur in the mucus-producing cells in the inner layer of colon. Carcinoid tumors, gastrointestinal stromal tumors and sarcomas

are the other types of colorectal cancer. The main symptoms of CRC are diarrhea, dis- comfort in the abdomen, anemia and fatigue. Age, race, gender, and a person’s family

history are the main risk factors in developing colorectal cancer. Various therapies pre- viously available to treat colorectal cancer includes chemotherapy, radiation therapy

and targeted therapy. All these existing therapies have some after-effects therefore, there is a need to develop an effective therapy for the treatment of colorectal cancer. In this research, we performed microarray and RNA-seq analysis to get differentially expressed genes of colorectal cancer. For this purpose, we used three Microarray and one RNA sequencing dataset that were obtained from publicly available databases. After getting DEGs we used David (The Database for Annotation, Visualization, and Integrated Discovery) tool to find out which differentially expressed genes are highly associated with colorectal cancer.AURKA gene from David tool was selected for further analysis. According to literature, AURKA gene is upregulated in colorectal cancer and overexpression of this gene causes CRC cell progression and proliferation. Furthermore, we performed the docking of Auorora Kinase A (AURKA) protein with 220 FDA-approved anticancer drugs that were chosen as ligands. The anti-cancer

drugs such as Dactinomycin, Dutasteride, Lumacaftor, Alectinib, Daridorexan, Can- desartan, Tonabersat, Ziconotide, Camptothecin, and Diamorphine show excellect

binding interactions with Auorora Kinase A protein.