GALNT6 Knockdown Inhibits the Proliferation and Migration of Colorectal Cancer Cells and Increases the Sensitivity of Cancer Cells to 5-FU

Abstract

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.

Reduced expression of alanyl aminopeptidase is a robust biomarker of non‐familial adenomatous polyposis and non‐hereditary nonpolyposis colorectal cancer syndrome early‐onset colorectal cancer

“…Recent studies have reported that GALNT6 is highly upregulated in CRC tissues. 45 , 46 In addition, GalNAc‐Ts have been reported to influence several tumorigenic processes, including immune evasion, invasion, EMT induction, and metastasis. 46 , 47 , 48 Moreover, a low expression of TFF2 and TFF3, which were predicted to be inhibited by GALNT6, have been reported to associate with gastric cancer.…”

“…This analysis predicted that GALNT6 (polypeptide N‐acetylgalactosaminyltransferase 6; GalNAc‐T6) was activated in EOCRC where it inhibited ANPEP expression. Recent studies have reported that GALNT6 is highly upregulated in CRC tissues 45,46 . In addition, GalNAc‐Ts have been reported to influence several tumorigenic processes, including immune evasion, invasion, EMT induction, and metastasis 46–48 .…”

Epigenomic reprogramming of therapy-resistant circulating tumor cells in colon cancer

“…Moreover, COL9A3 promotes epithelial-to-mesenchymal transition, invasion, and migration in gastric cancer (Wu et al, 2021). GALNT6 overexpression has been associated in CRC with resistance to fluoropyrimidines and CRC cell proliferation and migration (Peng et al, 2021). This gene is also involved in the activation of the PI3K/AKT signaling pathway and in breast cancer cell migration and invasion (Liu et al, 2020).…”

Low expression of GALNT6 gene in gliomas promotes immune infiltration and improves tumor prognosis using bioinformatics analysis

“…Bioinformatics studies can often produce more accurate results for microarray testing of glioma samples based on large sample data. According to recent research, the expression of the GALNT6 gene has been linked to the proliferation, migration, and drug sensitivity of tumors 13 .…”