Aberrant expression of MYD88 via RNA‐controlling CNOT4 and EXOSC3 in colonic mucosa impacts generation of colonic cancer

Abstract

In 2020, the worldwide incidence and mortality of colorectal cancer (CRC) were third and second, respectively. As the 5‐y survival rate is low when CRC is diagnosed at an advanced stage, a reliable method to predict CRC susceptibility is important for preventing the onset and development and improving the prognosis of CRC. Therefore, we focused on the normal colonic mucosa to investigate changes in gene expression that may induce subsequent genetic alterations that induce malignant transformation. Comprehensive gene expression profiling in the normal mucosa adjacent to colon cancer (CC) compared with tissue from non‐colon cancer patients was performed. PCR arrays and qRT‐PCR revealed that the expression of 5 genes involved in the immune response, including MYD88, was increased in the normal mucosa of CC patients. The expression levels of MYD88 were strikingly increased in precancerous normal mucosa specimens, which harbored no somatic mutations, as shown by immunohistochemistry. Microarray analysis identified 2 novel RNA‐controlling molecules, EXOSC3 and CNOT4, that were significantly upregulated in the normal mucosa of CC patients and were clearly visualized in the nuclei. Forced expression of EXOSC3 and CNOT4 in human colonic epithelial cells increased the expression of IFNGR1, MYD88, NFκBIA, and STAT3 and activated ERK1/2 and JNK in 293T cells. Taken together, these results suggested that, in the inflamed mucosa, EXOSC3‐ and CNOT4‐mediated RNA stabilization, including that of MYD88, may trigger the development of cancer and can serve as a potential predictive marker and innovative treatment to control cancer development.

Identification of Cancer Driver Genes by Integrating Multiomics Data with Graph Neural Networks

“… 0.02103 [ 37 ] LUSC EXOSC3 In inflamed mucosa, EXOSC3 and CNOT4-mediated RNA stabilization, including that of MYD88, may trigger cancer development and could serve as potential predictive markers and innovative therapies to control cancer progression. 0.00055 [ 57 ] KRR1 Tumor-associated antigens KRR1 and ZRF1 and their cognate autoantibodies may be considered as potential molecular markers for breast cancer. 0.0318 [ 58 ] LUAD ATP6V0B miRNA-15a, which could regulate ATPase, H(+) transporting, lysosomal21 kDa, V0 subunit b(ATP6V0B), and miRNA-155, were found to be the most significant.…”

Integrated Bioinformatic Investigation of EXOSCs in Hepatocellular Carcinoma Followed by the Preliminary Validation of EXOSC5 in Cell Proliferation

“…It has been reported that EXOSC1 could cleave single-stranded DNA and sensitize human kidney renal clear cell carcinoma cells to poly (ADP-ribose) polymerase inhibitors [ 11 ]. Additionally, the enhancing expression of EXOSC2 directly regulated by tRNAGluUUC is closely related to breast cancer metastasis [ 12 ], while EXOSC3 and EXOSC4 can trigger the development of colonic and colorectal cancer, respectively [ 13 , 14 ]. Similarly, EXOSC5, EXOSC8, EXOSC9 and EXOSC10 are also remarkably involved in the progression of various cancers, but there is no evidence to show the association between EXOSC6/7 and cancers at present.…”