MiR-433-3p Inhibits Proliferation and Invasion of Esophageal Squamous Cell Carcinoma by Targeting GRB2

Abstract

Background/Aims: MicroRNAs (miRNAs) are non-coding single stranded RNAs of 17-25 nucleotides in size, and their altered expression has been observed in various cancers. Previous studies have confirmed that miR-433-3p has effects on cancer cell proliferation, invasion, and migration, and its expression also correlates with sensitivity to chemotherapy. However, to date, there have been no studies on the biological functions of miR-433-3p in esophageal squamous cell carcinoma (ESCC). Methods: The Cell Counting Kit-8, transwell, and matrigel assays were used to test the effects of miR-433-3p and its predicted target, growth factor receptor-bound protein 2 (GRB2), on the proliferation, migration, and invasion of Eca109 and KYSE30 cells, two types of esophageal cancer cell lines. The miR-433-3p binding site in the 3′ untranslated region (UTR) region of GRB2 was predicted and verified using miRNA target site prediction software and structuring correct mutant examination. Western blotting and fluorescent quantitative PCR (FQ-PCR) techniques were employed to evaluate GRB2 expression. The inhibitory effects of miR-433-3p on tumor growth were investigated using a tumor xenograft model. Results: The binding site of miR-433-3p was identified in the 3′UTR region of GRB2. Western blotting and FQ-PCR showed that miR-433-3p inhibited the mRNA and protein expression of GRB2. Overexpression of GRB2 inhibited tumorigenesis in nude mice. MiR-433-3p overexpression inhibited the proliferation, migration, and invasion of ESCC cells by suppressing GRB2 gene expression. Conclusions: Our findings suggest that targeting miR-433-3p may have therapeutic benefits in ESCC.

KPNA2-Associated Immune Analyses Highlight the Dysregulation and Prognostic Effects of GRB2, NRAS, and Their RNA-Binding Proteins in Hepatocellular Carcinoma

“…Fredericks and Ren, 2013). Recently, its tumor-promoting effects were shown in many malignancies including lung cancer (Yang et al, 2017a;Jiang et al, 2018;Mitra et al, 2018;Wang and Wang, 2020), gastric cancer (Ye et al, 2018), colorectal cancer (Ding et al, 2019), ovarian carcinoma (Huang et al, 2018), renal cell carcinoma (Gu et al, 2017), breast cancer (Lim et al, 2000;Haines et al, 2014;López-Cortés et al, 2020), and esophageal squamous cell carcinoma (Shi et al, 2018). In addition, in lung cancer (Chen et al, 2020), ovarian cancer (Xu et al, 2018), colorectal cancer (Agrawal et al, 2019), and breast cancer (Chen et al, 2018), its associations with the resistance of the tumors to chemotherapeutic drugs were presented, and its downregulation could reverse the resistant status or enhance the sensitivity to the drugs, indicating its potential as a chemotherapeutic target in the malignancies.…”

Emerging Role of Non-Coding RNAs in Esophageal Squamous Cell Carcinoma

“…Many such studies have been published so far, which reveal miRNAs as tumor suppressors or oncogenes (Table 1). For example, miR-146a, miR-133b, miR-106b-3p, miR-219-5p, miR-206, miR-384, miR-455-5p, miR-128, miR-145-3p/5p, miR-10b-3p, miR-874-3p, miR-10a, miR-365, miR-301a, miR-6775-3p, miR-139-5p, miR-516b, miR-449a-5p, miR-125b, miR-433-3p, miR-370, miR-133b, miR-30a-3p/5p, miR-34a, miR-196a, and miR-125b-5p have been shown to act as tumor suppressors by inhibiting ESCC cell proliferation, promoting apoptosis by directly targeting oncogenes, or antagonizing pro-cancer signaling pathways [29,33,35,[40][41][42][43][44][45][46][47][48][49][50][51][52][54][55][56][57][58][60][61][62][63]110,133]. In contrast, pro-oncogenes such as miR-141, miR-21, miR-10b-3p, miR-424, miR-675-3p, miR-543, miR-135, miR-23b-3p, miR-502, miR-21-5p, and miR-548k have been reported to play contrasting roles in promoting cell proliferation or suppressing apoptosis in ESCC [47,[64][65][66][67][68][69][70][71][72][73].…”

Functional Significance and Therapeutic Potential of miRNA-20b-5p in Esophageal Squamous Cell Carcinoma

“…18 For miR-138 and miR-145, downregulated miRNA expression levels in ESCC tissue have been pointed out. [19][20][21][22][23][24] In comparison, miR-21, miR-200c, and miR-133a were upregulated with the presence of esophageal malignancy. 25,26 Multiple miRNAs, namely miR-10, miR-182, miR-338-3p, and miR-708-5p, had positive associations with the advanced tumor stages of non-small cell lung cancer (NSCLC), as well as with lymph node metastasis.…”