miR-92a-3p promotes the proliferation and invasion of gastric cancer cells by targeting KLF2.

MicroRNAs (miRNAs) have pivotal roles in the initiation and progression of gastric cancer (GC), and miR-92a-3p has been proved to act as an oncogene in multiple malignancies. However, the molecular mechanisms by which miR-92a-3p contributes to GC remain unclear. The differentially expressed miRNAs were screened by GEO dataset, and the association of miR-92a-3p expression with clinicopathological characteristics and prognosis in patients with GC was analyzed by TCGA dataset. The target genes of miR-92a-3p were identified by bioinformatic analysis, and their interaction was confirmed by luciferase reporter assay. MTT, EdU and Transwell assays were conducted to determine the role of miR-92a-3p in GC cells. As a result, it was found that the expression levels of miR-92a-3p were increased in GC tissues and were associated with tumor size, lymph node infiltration and distant metastasis, acting as an independent prognostic factor of poor survival in patients with GC. Restored expression of miR-92a-3p facilitated cell proliferation, DNA synthesis and cell invasion, but its inhibitor reversed these effects. KLF2 was further identified as a direct target of miR-92a-3p, indicating a negative correlation with miR-92a-3p expression and harboring a favorable prognosis in GC. In addition, KLF2 repressed cell proliferation and invasion and attenuated the tumor-promoting effects of miR-92a-3p in GC cells. Altogether, our findings demonstrated that miR-92a-3p promoted the proliferation and invasion of GC cells by targeting KLF2.

Krüppel-like factor 2 suppresses growth and invasion of gastric cancer cells in vitro and in vivo.

Krüppel-like factor 2 (KLF2), a novel tumor-suppressor gene, is implicated in diverse cellular processes, including cell growth, apoptosis, and invasion. However, the role and action mechanisms of KLF2 in gastric cancer (GC) need be further elucidated. The expression of KLF2 was investigated by immunohistochemical assay in human GC tissues, and lentivirus-mediated KLF2 overexpression was transfected into GC cells (AGS and HGC-27) for assessing cell proliferation and invasion, respectively indicated by MTT and Transwell assays. Subcutaneous GC tumor models were constructed for estimating tumor growth in vivo. As a result, the expression level of KLF2 was decreased in GC tissues compared with the para-carcinoma tissues (31.03% vs 53.45%, P=0.035), and negatively correlated with the lymph node metastasis in GC patients (P=0.02). Moreover, overexpression of KLF2 inhibited the cell proliferation and invasive potential and downregulated the protein expression of PCNA, Bcl-2 and MMP-9 in GC cells. The result in vivo showed KLF2 overexpression reduced the xenograft tumor growth. In conclusion, our findings indicate that KLF2 may function as a tumor suppressor involved in the progression of human GC.