microRNA‑144 inhibits cell proliferation and invasion by directly targeting TIGAR in esophageal carcinoma

Abstract

microRNAs (miRNAs) have been identified to play vital roles in the development and progression of numerous different types of human malignancy, including esophageal squamous cell carcinoma (ESCC). In the present study, the biological function of microRNA-144 (miR-144) was investigated, as well as its underlying molecular mechanism in ESCC. The results revealed that miR-144 expression was significantly decreased, whereas the expression of TP53-inducible glycolysis and apoptosis regulator (TIGAR) was significantly increased in human ESCC tissues when compared with adjacent non-tumor tissues. An increase in TIGAR was significantly associated with tumor size and Tumor-Node-Metastasis staging in patients. Functional analysis revealed that the overexpression of miR-144 using lentivirus particles significantly inhibited cell proliferation and tumor colony formation, and induced cell apoptosis in EC9706 and EC109 cells. The autophagy activity was also enhanced by miR-144 activity. In addition, overexpression of miR-144 significantly inhibited tumor growth in vivo. In the present study, TIGAR was confirmed to be the downstream target of miR-144 in ESCC. siRNA-mediated downregulation of TIGAR inversely regulated the inhibition effect of miR-144 on ESCC cells. To conclude, the present study demonstrated that miR-144 inhibits proliferation and invasion in esophageal cancer by directly targeting TIGAR.

MicroRNAs and Corresponding Targets in Esophageal Cancer as ShownIn VitroandIn Vivoin Preclinical Models

“…Proliferation of EC9706 and ECA109 ESCCs was inhibited by miR-144, which was associated with a pro-apoptotic effect (169). In vivo, miR-144 inhibited tumor growth of xenografts of these cell lines (169). TIGAR was identified as a direct target of miR-144 (169).…”

“…with ESCC and correlated with poor prognosis (169). Proliferation of EC9706 and ECA109 ESCCs was inhibited by miR-144, which was associated with a pro-apoptotic effect (169). In vivo, miR-144 inhibited tumor growth of xenografts of these cell lines (169).…”

“…In vivo, miR-144 inhibited tumor growth of xenografts of these cell lines (169). TIGAR was identified as a direct target of miR-144 (169). TIGAR acts as a fructose-2,6 biphosphatase and as a regulator of glucose breakdown (170).…”

MicroRNA-144: A novel biological marker and potential therapeutic target in human solid cancers

“…By targeting p53-induced glycolysis and apoptosis regulator (TIGAR), miR-144 was shown to inhibit proliferation, induced apoptosis, and increased autophagy in both A549 and H460 cells. Through the targeting of TIGAR, miR-144 was also shown to suppress esophageal squamous cell carcinoma (ESCC) cell proliferation [21]. Likewise, evidence demonstrated an obvious down-regulation of miR-144 in non-small cell lung cancer (NSCLC) tissues and cells, which was able to inhibit cell growth as well as facilitate apoptosis through down regulation of ZFX protein expression [22].…”

Itchy E3 ubiquitin-protein ligase promotes neuroblastoma progression in vitro and in vivo

“…Recent studies have found that there are a wide variety of miRNAs in animals and plants, and their functions cover almost all phenomena in the biological field [18] . The main function of miRNA is to target messenger RNA (mRNA) and induce its degradation, thereby regulating gene expression level at the post-transcriptional level [19][20][21] . This process is the key to regulating cell growth, differentiation, apoptosis, and proliferation, and is an important way to regulate tumorigenesis and development.…”