MicroRNA‑214 suppresses the viability, migration and invasion of human colorectal carcinoma cells via targeting transglutaminase 2

Abstract

Colorectal carcinoma (CRC) is a common malignancy of the digestive tract. MicroRNA (miR)-214 is considered a key hub that controls tumor networks; therefore, the effects of miR-214 on CRC were examined and its target gene was investigated in this study. The expression levels of transglutaminase 2 (TGM2) and miR-214 were detected in CRC and adjacent normal tissues by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting, and luciferase activity was analyzed by dual luciferase reporter analysis. In addition, cell viability, invasion and migration were measured by Cell Counting kit-8 and Transwell assays, respectively. The expression levels of epithelial-mesenchymal transition-related proteins, and phosphoinositide-3 kinase (PI3K)/protein kinase B (Akt) signaling-associated factors were detected using RT-qPCR and western blotting. The results demonstrated that miR-214 expression was downregulated in CRC tissue, whereas TGM2 expression was upregulated. According to TargetScan prediction, miR-214 possesses a binding site to TGM2. In addition, transfection with miR-214 mimics markedly suppressed the viability of LoVo cells. miR-214 overexpression also inhibited cell invasion and migration by increasing E-cadherin and tissue inhibitor of metalloproteinases-2 expression, and decreasing matrix metalloproteinase (MMP)-2 and MMP-9 expression. Furthermore, miR-214 downregulated phosphorylation of PI3K and Akt; however, the expression levels of total PI3K and Akt were not affected by miR-214. In conclusion, this study indicated that TGM2 was a target gene of miR-214, and a negative correlation between miR-214 and TGM2 expression was determined in CRC. Notably, miR-214 markedly suppressed the viability, invasion and migration of CRC cells, which may be associated with a downregulation in PI3K/Akt signaling. These findings suggested that miR-214 may be considered a novel target for the treatment of CRC.

MicroRNA‑125a‑5p regulates liver cancer cell growth, migration and invasion and EMT by targeting HAX1

“…The upstream target of HAX1 in the progression of liver cancer was examined. different miRNAs may participate in the control of a same mRNA molecule (38). Bioinformatics analysis predicted that both miR-125a-5p and miR-223-3p could bind to HAX1.…”

Exosomal circEIF3K from cancer-associated fibroblast promotes colorectal cancer (CRC) progression via miR-214/PD-L1 axis

“…A number of studies showed that miRNAs were dysregulated in various types of cancer cells [ 12 , 13 ]. MiR-214 has been demonstrated to inhibit HCC [ 14 ], bladder cancer [ 15 ] and CRC [ 16 ] progression. Thus, we hypothesized that miR-214 might be potential target of circEIF3K in CRC.…”

Hypoxia-Dependent Expression of TG2 Isoforms in Neuroblastoma Cells as Consequence of Different MYCN Amplification Status

“…It has been reported that an increase of TG2 expression confers a growth advantage to cancer cells, enabling them to survive in hypoxic conditions. TG2 overexpression seems to be associated with the proliferation and metastasis of various tumours, such as breast cancer, ovarian cancer, lung cancer and colorectal carcinoma [32][33][34][35][36]. Several reports proposed TG2 inhibition as a useful tool for therapeutic approaches.…”

“…For example, it has been reported that the GK921 TG2 inhibitor, overlapping with the p53-binding site of TG2, was able to induce apoptosis in renal cell carcinoma [37]. Similarly, the inhibition of TG2 by the microRNA (miR)-214 was associated with a relevant suppression of viability, invasion and migration of colorectal carcinoma cells [36].…”