DNMT1 maintains the methylation of miR‐152‐3p to regulate TMSB10 expression, thereby affecting the biological characteristics of colorectal cancer cells

Abstract

Objective: DNA methyltransferases (DNMTs) take on a relevant role in epigenetic control of cancer proliferation and cell survival. However, the molecular mechanisms underlying the establishment and maintenance of DNA methylation in human cancer remain to be fully elucidated. This study was to investigate that how DNMT1 affected the biological characteristics of colorectal cancer (CRC) cells via modulating methylation of microRNA (miR)-152-3p and thymosin β 10 (TMSB10) expression. Methods: DNMT1, miR-152-3p, and TMSB10 expression, and the methylation of miR-152-3p in CRC tissues and cells were detected. SW-480 and HCT-116 CRC cells were transfected with DNMT1 or miR-152-3p-related sequences or plasmids to explore their characters in biological functions of CRC cells. The binding relationship between DNMT1 and miR-152-3p and the targeting relationship between miR-152-3p and TMSB10 were analyzed. The tumor growth was also detected in vivo. Results: Upregulated DNMT1, TMSB10, reduced miR-152-3p, and methylated miR-152-3p were detected in CRC tissues and cells. Silenced DNMT1 or upregulated miR-152-3p reduced TMSB10 expression and suppressed CRC progression and tumor growth. Moreover, elevated DNMT1 could reverse the effect of miR-152-3p upregulation on CRC development and tumor growth. DNMT1 maintained methylation of miR-152-3p. TMSB10 was the direct target gene of miR-152-3p. Conclusion: The study highlights that silenced DNMT1 results in nonmethylated miR-152-3p to depress TMSB10 expression, thereby inhibiting CRC development, which provides a new approach for CRC therapy.

Expression and Clinical Significance of HER2 Gene and DNMT1 in Non-Small-Cell Lung Cancer

“…Epidermal growth factor receptor 2 (HER2) and human epidermal growth factor receptor 3 (HER3) belong to the receptor tyrosine kinase (RTK) superfamily, both of which can produce heterodimers to participate in tissue signal transduction, endangering cell differentiation, erosion, differentiation, and migration [ 3 , 4 ]. DNA methyltransferase 1 (DNMT1) is the most abundant methyltransferase in cells, and its role is to maintain DNA methylation [ 5 , 6 ]. The abnormal expression of DNMT1 and HER2 genes may cause the loss of tumor suppressor gene function and the increase of protooncogene activity, which play a key role in the development trend of various malignant tumors [ 7 ].…”

Hsa_circ_0040809 regulates colorectal cancer development by upregulating methyltransferase DNMT1 via targeting miR‐515‐5p

“…33,34 Silencing DNMT1 inhibits the proliferation, migration, and invasion, and induces apoptosis of CRC cells in vitro, and reduces tumor volume and weight in nude mouse. 18 As key regulators that inhibit mRNA translation and promote mRNA degradation, miRNAs are promising inhibitors of DNMT1. Previous studies have confirmed that miR-152 and miR-185-5p can inhibit DNMT1 expression in cancer cells.…”

“…17 DNA methyltransferase 1 (DNMT1) features prominently in epigenetic modification. 18 A study has demonstrated that DNMT1 is highly expressed in CRC and facilitates the methylation of multiple tumor-suppressive genes. 19 However, the upstream mechanism of abnormal DNMT1 expression remains unknown.…”

Comprehensive Analysis of Prognostic and Genetic Signatures for General Transcription Factor III (GTF3) in Clinical Colorectal Cancer Patients Using Bioinformatics Approaches

“…Statistical options for the ClueGO/CluePedia enrichment analysis were set based on a hypergeometric test that is two-sided with p ≤ 0.05, the Benjamini-Hochberg correction, and a kappa score of ≥2 as the primary criteria. Through Cytoscape analysis (GlueGO and CluePedia), we found that members of the GTF3 gene family have a high correlation with metastatic markers such as ABL1 [46,47], WDR6 [48], ARAP1-AS1 [49,50], DNMT1 [51][52][53][54][55], FASN [56,57] (Figure 6D).…”