MicroRNA-133b Inhibits nTumor Cell Proliferation, Migration and Invasion by Targeting SUMO1 in Endometrial Carcinoma

Abstract

Objectives: An increasing number of studies have confirmed that microRNAs (miRNAs/miRs), as oncogenes or tumor suppressor genes, play an important regulatory role in the occurrence and development of numerous types of cancer. The aim of the present study was to investigate the potential role and mechanism of miR-133b and small ubiquitin like modifier 1 (SUMO1) in the development of endometrial carcinoma (EC). Methods: First, Venn diagrams are used to identify the differential expressions of miRNAs in EC from GSE35794 and GSE25405 datasets. Next, we conduct a series of functional tests, including Cell Counting Kit-8, wound healing, and transwell and matrigel assays. Then, a bioinformatics tool, is used to identify downstream target genes of miR-133b and to verify the predicted results by RT-qPCR, Western blotting and double luciferase reporter gene analysis. Finally, in order to further study whether the cellular function of miR-133b is mediated by the expression of SUMO1, rescue experiments were carried out. Results: The results of bioinformatics studies showed that the expression of miR-133b was down-regulated in EC tissues, and the expression level of miR-133b was lower in patients with high grade, different histology or menopausal status. The results of functional assay showed that overexpression of miR-133b reduced cell proliferation, migration and invasion. On the contrary, miR-133b silence has the opposite effect. SUMO1 was the direct target of miR-133b and was negatively regulated by miR-133b. The decrease of SUMO1mRNA expression inhibited the proliferation, migration and invasion of EC cells, and reversed the effect of miR-133b on EC cells. Conclusion: The findings from the present study suggested that miR-133b may be a tumor suppressor gene and a potential therapeutic target for the treatment of EC.

Cx43‐mediated sorting of miRNAs into extracellular vesicles

“…Being cells from different origins—HEK293 is an embryonic kidney cell line, while C33 is a tumor epithelial cell line—it is likely that both biological functions and signals that govern miR‐133b secretion are different. For example, miR‐133b acts as a tumor suppressor in various cancers, including endometrial carcinoma, being its levels diminished in tumor cells‐derived EV (Cai et al , 2020; Liao et al , 2021). On the other hand, an increase of miR‐133b is implicated in renal disease (Sun et al , 2018).…”

Navigating the genomic instability mine field of osteosarcoma to better understand implications of non-coding RNAs

“…Few other miRNAs have been found targeting the histone modifying enzymes such as HDAC4 or Sirtuin-1 and thus inhibiting proliferation, migration, invasion and epithelial-mesenchymal transition of osteosarcoma cells, for example, miR-126, miR-133b, miR-204 ( Liao et al, 2021 ; Shi et al, 2017 ; Tang et al, 2017 ; Ying et al, 2017 ). Tumor suppressor miR-449a and miR-449b were epigenetically repressed in the osteosarcoma cell line via H3K27me3 resulting in E2F1 deregulation.…”