MicroRNA-143-3p, up-regulated in H. pylori-positive gastric cancer, suppresses tumor growth, migration and invasion by directly targeting AKT2

Abstract

Our previous studies have suggested a protective role for H. pylori infection in the prognosis of gastric cancer. Based on those findings, we hypothesized that H. pylori-positive and -negative gastric cancers may exhibit different growth patterns and pathobiological behaviors, indicating different mechanisms of cancer progression. By microarray analysis, we studied miRNAs expression profiles in 42 gastric cancer patients, comparing 21 H. pylori-positive and 21 H. pylori-negative groups. Luciferase reporter assay and western blot were used to examine the potential target genes of the interested miRNA. In the present study, 53 miRNAs were significantly differentially expressed in H. pylori-positive and -negative gastric cancer tissues. We investigated the expression and function of one candidate, miR-143-3p, which was the most significantly increased miRNA in H. pylori-positive gastric cancer tissues. We observed that miR-143-3p expression was significantly decreased in gastric cancer tissues and cells, which correlated with late stage and lymph node metastasis. Using gain- and loss-of-function experiments in vitro, we demonstrate that miR-143-3p negatively regulated cell growth, apoptosis, migration and invasion. We further characterized AKT2 as a novel direct target of miR-143-3p. Knockdown of AKT2 expression mimicked the effects of miR-143-3p restoration. In conclusion, our data suggest that miR-143-3p acts as a novel tumor suppressive miRNA by regulating tumor growth, migration and invasion through directly targeting AKT2 gene. Further investigation is warranted to characterize the mechanisms underlying gastric cancer progression and may eventually contribute to its therapy.

Upregulation of lncRNA ADAMTS9-AS2 Promotes Salivary Adenoid Cystic Carcinoma Metastasis via PI3K/Akt and MEK/Erk Signaling

“…miR-143-3p was reported to be upregulated in H. pylori-positive gastric cancer, and it suppressed tumor proliferation, migration, and invasion by directly targeting AKT2. 17 However, miR-143-3p was also found to be downregulated in esophageal squamous cell carcinoma and ovarian carcinoma, and it contributed to cancer progression. 17,30,31 miR-143-3p was induced by p53, and an excess of miR-143-3p prevented the induction of MDM2, BTG2, and CDKN1A mRNA and/or protein.…”

“…Previous studies have shown that six miRNAs, miR-2392, miR-362-5p, miR-193a-5p, miR-143-3p, miR-493-5p, and miR-600, were closely associated with invasion and cancer metastasis. [14][15][16][17][18][19] Then we used qRT-PCR to validate the expression levels of six miRNAs in SACC cells after transfection. Our results showed that the expression levels of miR-193a-5p and miR-143-3p were significantly upregulated in SACC-LM cells when ADAMTS9-AS2 was deleted, yet miR-193a-5p and miR-143-3p were downregulated in SACC-83 cells when ADAMTS9-AS2 was overexpressed, indicating a potentially competing relationship between the ADAMTS9-AS2 and miR-193a-5p or miR-143-3p ( Figures S2A and S2B).…”

MicroRNA‐143‐3p inhibits colorectal cancer metastases by targeting ITGA6 and ASAP3

“…MicroRNAs are known to carry out their biological functions through regulating the protein expression of downstream target genes, thus affecting the occurrence and development of tumors. To date, a number of possible target genes have been identified for miR-143-3p including quaking I-5 protein (QKI-5), 13 AKT serine/threonine kinase 2 (AKT2), 14 mitogen-activated protein kinase 7 (MAPK7), 15 and DNA methyltransferase 3A (DNMT3A). 16 In this study, we used bioinformatics software to predict 108 possible target genes of miR-143-3p and by real-time quantitative PCR confirmed that the expression levels of both As a transmembrane glycoprotein-adhering receptor, ITGA6 mediates cell-matrix and cell-cell adhesion.…”

Pathogenesis of Helicobacter pylori infection

“…Among 53 different miRNAs, the expression of miR‐143‐3p was the most significantly upregulated in H. pylori (+) gastric cancer tissues. In vitro assays revealed a negative regulation on cell growth, apoptosis, invasion, and migration, showing that miR‐143‐3p acts as tumor suppressor miRNA by targeting AKT2 . Regarding H. pylori ‐related virulence factors, Zou et al.…”

“…In vitro assays revealed a negative regulation on cell growth, apoptosis, invasion, and migration, showing that miR-143-3p acts as tumor suppressor miRNA by targeting AKT2. 46 Regarding H. pylori-related virulence factors, Zou et al demonstrated that Tipα, a carcinogenic factor of H. pylori, activated NF-κB by inhibiting the miR-3178-mediated targeting of TRAF3. 47 MiR-124 has tumor suppressive functions and is regulated by CpG methylation silencing.…”