MicroRNA-93 promotes proliferation and metastasis of gastric cancer via targeting TIMP2

Abstract

MicroRNAs (miRNAs) are important regulators of pathobiological processes in various cancer. In the present study, we demonstrated that miR-93 expression was significantly up-regulated in gastric cancer tissues compared with that in matched normal mucosal tissues. High expression of miR-93 was significantly associated with lymph node metastasis and tumor-node-metastasis (TNM) stage. Functionally, ectopic expression of miR-93 promoted cell proliferation, migration, invasion, EMT phenotypes, and repressed apoptosis and G1 cell cycle arrest in vitro, and promoted tumor formation in vivo. We further identified that tissue inhibitor of metalloproteinase 2 (TIMP2) was a direct target of miR-93 by using luciferase reporter assay, qRT-PCR, and immunoblotting assay. Furthermore, knockdown of TIMP2 with specific siRNA showed similar oncogenic effects in gastric cancer cells with that transfected with miR-93 mimics. Our findings indicated that miR-93 serves as a tumor promoter in human gastric carcinogenesis by targeting TIMP2, suggesting that miR-93 might be a promising biomarker and therapeutic target for treatment of gastric cancer.

Retracted: Knockdown of long noncoding RNA urothelial carcinoma–associated 1 inhibits cell viability, migration, and invasion by regulating microRNA‐182 in gastric carcinoma

“…30,31 Li et al 32 reported that miR-182 was downregulated in GC tissues and it could suppress proliferation and migration of GC cells via targeting Kruppel-like factor 4. In addition, Guan et al 36 reported that miR-93 increased GC cells' proliferation and metastasis by targeting TIMP2. 33,34 One study from Zhu et al 35 found that miR-106a could promote GC cells' proliferation and triggered cell metastasis by targeting TIMP2.…”

Expression Levels of microRNAs miR-93 and miR-200a in Pancreatic Adenocarcinoma with Special Reference to Differentiation and Relapse-Free Survival

“…Similarly, in breast cancers, miR-93 has been found to decrease multiple carcinogenic processes, interestingly, in an Nrf2-dependent manner [23]. On the other hand, in some malignancies, such as gastric cancer, hepatocellular carcinoma, non-small-cell lung cancer, osteosarcoma, ovarian cancer, and gliomas, miR-93 down-regulates tumour suppressor (mostly PTEN) expression and has consequently been linked to more aggressive cancer phenotypes in both experimental and clinical studies [38-43]. …”

Droplet digital PCR-based circulating microRNA detection serve as a promising diagnostic method for gastric cancer

“…Some studies have reported that high levels of miR-21 expression may induce tumor proliferation, migration and invasion via the downregulation of Noxa or PTEN expressions in GC cells [ 33 , 34 ]. And miR-93 could promote proliferation and metastasis of GC via targeting TIMP2 or inactivation of the Hippo signaling pathway [ 35 , 36 ]. In cancer-associated fibroblasts from GC, miR-106b could promote cell migration and invasion by targeting PTEN [ 37 ].…”