Retracted: MicroRNA‐133a inhibits gastric cancer cells growth, migration, and epithelial‐mesenchymal transition process by targeting presenilin 1

Abstract

Gastric cancer (GC) is one of the most common malignancies and a leading cause of cancer-related death worldwide. Accumulating evidence reported that microRNA (miR)-133a was involved in GC. This study aimed to investigate the function and mechanism of miR-133a in the development and progression of GC. The expression of miR-133a and presenilin 1 (PSEN1) in two GC cell lines, SGC-7901 and BGC-823, were inhibited and overexpressed by transient transfections. Thereafter, cell viability, migration, and apoptosis were measured by trypan blue exclusion assay, transwell migration assay, and flow cytometry assay, respectively. Dual-luciferase reporter assay was conducted to verify whether PSEN1 was a direct target of miR-133a. Furthermore, quantitative real-time polymerase chain reaction and Western blot analysis were mainly performed to assess the expression changes of epithelial-mesenchymal transition (EMT)-associated proteins, apoptosis-related proteins, and Notch pathway proteins. MiR-133a inhibitor significantly increased cell viability and migration, while miR-133a mimic decreased cell viability, migration, and induced apoptosis. miR-133a suppression accelerated transforming growth factor-β1 (TGF-β1)-induce EMT, as evidenced by upregulation of E-cadherin, and downregulation of N-cadherin, vimentin, and Slug. Of contrast, miR-133a overexpression blocked TGF-β1-induce EMT by altering these factors. PSEN1 was a direct target of miR-133a, and suppression of PSEN1 abolished the promoting functions of miR-133 suppression on cell growth and metastasis. Moreover, PSEN1 inhibition decreased Notch 1, Notch 2, and Notch 3 protein expressions. This study demonstrates an antigrowth and antimetastasis role of miR-133a in GC cells. Additionally, miR-133a acts as a tumor suppressor may be via targeting PSEN1.

Emerging roles of MiR-133a in human cancers

“…Also in GC line SGC-7901 and BGC-823, miR-133a played an antigrowth and antimetastasis role by inhibiting transforming growth factor-beta1 (TGF-beta1)-induced EMT via targeting PSEN1. Moreover, the decrease of PSEN1 could further downregulate Notch 1, Notch 2, and Notch 3 [35]. MiR-133a could not only suppress cell proliferation, induce cell cycle arrest at G0/G1 stage and accelerate cell apoptosis, but also inhibit cell migration and invasion in vivo and in vitro via targeting IGF-1R and negatively regulating downstream AKT and ERK signal pathway [36][37][38].…”

Hsa_circ_0046263 functions as a ceRNA to promote nasopharyngeal carcinoma progression by upregulating IGFBP3

“…The results indicated that miR-133a-5p expression was downregulated in NPC tissue samples. miR-133 is a proven "tumor suppressor gene" that is significantly downregulated in solid tumors, such as gastric cancer 14 , lung cancer 15 , and pancreatic carcinoma 16 . Next, we explored the function of miR-133a-5p in NPC cells.…”

Noncoding RNAs: the shot callers in tumor immune escape

“…5). For example, miR-133, 198 miR-141, 199 lncRNA ANRIL, 200 and lncRNA 00974 201 regulate the expression of TGF-β; Let-7, 202 miR-141, and the miR-200 family 203 target and regulate TGFBR Ι; miR-106b, 204 miR-17-5p, 205 miR-204, 206 miR-20a, 207 miR-21, 208 miR-590 209 and lncRNA MEG3 210 target and regulate TGFBR II; miR-141, miR-200a/c, miR-30d 203 and miR-155 211 regulate Smad2; miR-140 212 and lncRNA PVT1 213 regulate the expression of Smad3 and Smad4, respectively; and miR-21 regulates the expression of Smad7 in cervical cancer. 214 The abnormal expression of these ncRNAs in tumors can activate the TGF-β signaling pathway in different stages and then help tumors achieve immune escape by inhibiting a variety of immune cells, inducing the differentiation of immune cells and promoting EMT.…”