RETRACTED ARTICLE: Up-regulated miR-199a-5p in gastric cancer functions as an oncogene and targets klotho

Abstract

BackgroundRecent studies have shown that miR-199a-5p plays opposite roles in cancer initiation and progression of different cancer types, acting as oncogene for some cancer types but as tumor suppressor gene for others. However, the role and molecular mechanism of miR-199a-5p in gastric cancer are largely unknown.MethodsIn this study, miR-199a-5p expression level in gastric cancer was first analyzed by qPCRand then validated in 103 gastric cancer patients by in situ hybridization (ISH). Gastric cancer cell lines were transfected with miR-199a-5p inhibitor and mimic, and underwent in vitro transwell assays. Target genes (klotho) were identified using Luciferase reporter assay. Immunohistochemical staining was also used to investigate on how miR-199a-5p regulates the tumour-suppressive effects of klotho in gastric cancer.ResultsIn our present study, we found that miR-199a-5p level was significantly increased in gastric cancer tissues compared to paired normal tissues. We observed that miR-199a-5p could promote migration and invasion of gastric cancer cells. In situ hybridization of miR-199a-5p also confirmed that higher miR-199a-5p expression level was associated with increased likelihood of lymph node metastasis and later TNM stage. Luciferase reporter assay and immunohistochemistry revealed that klotho might be the downstream target of miR-199a-5p.ConclusionsOur present study suggests that miR-199a-5p acts as an oncogene in gastric cancer and functions by targeting klotho.

MicroRNA-199a-5p inhibits cisplatin-induced drug resistance via inhibition of autophagy in osteosarcoma cells

“…Hu et al reported that miR-199a-5p was frequently downregulated in colorectal cancer, which led to the upregulation of discoidin domain receptor 1 and the activation of epithelialto-mesenchymal transition-related signaling (16). In addition, the expression level of miR-199a-5p was significantly increased in gastric cancer tissues compared with paired normal tissues, and higher miR-199a-5p level was associated with increased lymph node metastasis and higher tumor-node-metastasis stage, suggesting that miR-199a-5p may act as an oncogene in gastric cancer (26). Recently, miR-199a-5p has been reported to exhibit inhibitory effects on autophagy (27).…”

The function of miR-199a-5p/Klotho regulating TLR4/NF-κB p65/NGAL pathways in rat mesangial cells cultured with high glucose and the mechanism

“…Moreover, the ectopic expression of p53 induces miR199a transcription, and then affects the restructuring of mouse embryonic fibroblasts (Wang et al, 2012). Recent research also found that miR-199a-5p can promote gastric cancer by inhibition of Klotho protein expression (He et al, 2014). Besides, can modulate the process of renal fibrosis (Christian et al, 2013) and the growth of kidney cancer cells (Tsukigi et al, 2012).…”

Identification of miR-199a-5p target genes in the skin keratinocyte and their expression in cutaneous squamous cell carcinoma

“…Another study also showed that miR-199a-5p was significantly down-regulated in advanced stage in small cell carcinoma of the cervix [34]. In contrast, expression of miR-199a-5p was increased in gastric cancer and it is associated with human gastric tumor development [12]. Similar with ovarian cancer and hepatocellular carcinoma, loss of miR-199a-5p expression may have an important role in pathogenesis of cSCC.…”

“…The miR-199a precursor produces mature miRNAs named miR-199a-5p and miR-199a-3p [9]. The results of several studies support a critical role for miR-199a in various cell types and tissues including the liver, stomach, ovary, and testis [10][11][12][13][14][15].…”