1. Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
2. Department of Gynaecology, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
3. Department of Gastrointestinal surgery, Xiangya hospital, Central south university, Changsha, 410013, Hunan, China.
The incidence of colorectal cancer (CRC) is increasing annually worldwide, highlighting the need for novel therapeutics to be developed. GALNT6 is a member of the N-acetylgalactosyltransferase enzyme family, which exhibits oncogenic functions in several types of cancers, such as breast cancer and ovarian cancer. However, the function of GALNT6 in CRC has not received much attention in recent years and is therefore poorly understood. In this study, the GALNT6 gene was screened using RNA-seq data obtained from The Cancer Genome Atlas (TCGA). RNA-seq data from 50 pairs of matched CRC patients in TCGA were obtained and analyzed, and the protein expression levels of GALNT6 were verified in 10 pairs of clinical samples. These samples showed that GALNT6 was highly expressed in CRC tissues. Functional analysis also showed that GALNT6 knockdown inhibited the proliferation and migration of CRC cells and increased the number of apoptotic cells. Furthermore, GALNT6 knockdown suppressed tumor growth in vivo. GALNT6 also regulated the AKT pathway based on ingenuity pathway analysis and western blotting assay. Finally, GALNT6 knockdown was observed to increase the sensitivity of CRC cells to 5-Fluorouracil (5-FU). These results, taken together, show that GALNT6 knockdown inhibits proliferation and migration of CRC cells and increases cellular sensitivity to 5-FU. It is therefore possible that targeting GALNT6 might prove to be an effective avenue for exploration in any attempt to develop new therapies for the treatment of CRC.
Keywords: GALNT6, colorectal cancer, AKT, drug sensitivity, 5-FU