MicroRNA-let-7 Targets HMGA2 to Regulate the Proliferation, Migration, and Invasion of Colon Cancer Cell HCT116

Abstract

Objective. To investigate the effect of microRNA-let-7 (miR-let-7) on the proliferation, migration, and invasion of colon cancer cell HCT116 in vitro and its regulatory mechanism on downstream HMGA2. Methods. It was planned to synthesize miR-let-7 overexpression (mimics) and interference expression (inhibitor) and transiently transfect colon cancer cell HCT116, detect the expression levels of miR-let-7 and HMGA2 in the cells after transfection and the targeted regulation effect of miR-let-7 on HMGA2, then detect the effect of upregulation/downregulation of miR-let-7 on HMGA2, and detect the proliferation, migration, and invasion of HCT116 cells. Results. The expression of miR-let-7 was downregulated, and the expression of HMGA2 was upregulated in HCT116. The expression of miR-let-7 increased significantly after HCT116 was transfected with miR-let-7 mimics. The expression of miR-let-7 decreased significantly after HCT116 was transfected with miR-let-7 inhibitor. The bioinformatics websites predicted that miR-let-7 has a binding site with HMGA2, and the dual-luciferase reporter gene experiment detected that miR-let-7 has a targeting relationship with HMGA2. The expression of HMGA2 decreased after HCT116 was transfected with miR-let-7 mimics; the expression of HMGA2 increased after HCT116 was transfected with miR-let-7 inhibitor. After upregulating miR-let-7, the proliferation, migration, and invasion ability of HCT116 was weakened. After miR-let-7 was inhibited, the proliferation, migration, and invasion ability of HCT116 was enhanced. Conclusion. Abnormal expression of miR-let-7 is an important factor affecting the proliferation, migration, and invasion of HCT116 cells, and it can promote or inhibit the biological behavior of cancer cells by targeting the expression of HMGA2. This study provides ideas for the drug development of new gene targets.

Identification and verification of m7G-Related genes as biomarkers for prognosis of sarcoma

“…m7G is the modification of RNA guanine (G) by adding methyl group at the 7th N position (Zhang et al, 2021), mostly in tRNA, rRNA, and mRNA 5'cap, which plays a crucial role in maintaining RNA processing, metabolism, stability, protein translation (Ramanathan et al, 2016). Through m7G alteration of Frontiers in Genetics frontiersin.org tRNA or miRNA, the METTL1/WDR4 complex influences the course of several malignancies, such as liver cancer (Li et al, 2022), lung cancer (Ma et al, 2021), and colon cancer (Chen and Liu, 2021). However, the role of m7G methylation modification in sarcomas remains unclear.…”

“…The methyltransferase-like 1 (METTL1) and WD repeat domain 4 (WDR4) complex, which was a member of m7GRGs, primarily governed the processing, metabolism, and function of RNA (Alexandrov et al, 2002;Malbec et al, 2019). m7G methylation of tRNA and miRNA played a crucial role in the occurrence and development of cancers, such as liver cancer (Li et al, 2022), lung cancer (Ma et al, 2021), and colon cancer (Chen and Liu, 2021). However, few investigations on m7GRGs in sarcomas have been conducted.…”

chi-miR-99b-3p Regulates the Proliferation of Goat Skeletal Muscle Satellite Cells In Vitro by Targeting Caspase-3 and NCOR1

“…Additionally, we found that several miRNAs, including miR-199c-3p, miR-199a-3p, let-7c-3p, let-7c-5p, miR-10a-5p, miR-125b-3p, and miR-99a-5p, were highly expressed in SMSCs after miR-99b-3p upregulation, and these have been reported to enhance muscle regeneration [ 27 , 28 , 29 , 30 ] or promote cell proliferation in some cancers [ 31 , 32 , 33 ]. Furthermore, miR-199c-3p, miR-199a-3p, miR-99a-3p, and miR-99b-3p belong to the same miRNA cluster, suggesting that overexpression of miR-99b-3p induces the expression of a series of cell cycle regulation related miRNAs, further promoting cell proliferation and differentiation in SMSCs.…”

Novel roles of METTL1/WDR4 in tumor via m7G methylation

“… 55 let-7e miRNA regulated the expression of HMGA2 negatively and then inhibited the proliferation, migration, and invasion of colon cancer cells. 56 In the meantime, the METTL1/WDR4 complex promoted the let-7e miRNA process in an m 7 G-dependent manner and overexpressed METTL1 -decreased HMGA2 by upregulating let-7e miRNA via m 7 G, inhibiting the progression of colon cancer. 19 , 57 …”