Identification of microRNA-124 in regulation of Hepatocellular carcinoma through BIRC3 and the NF-κB pathway

Abstract

MicroRNAs (miRNAs) being proved to be involved in the carcinogenesis of numerous tumors. MicroRNA-124 (miR-124), identified as a tumor suppressor, has been demonstrated to exert pivotal roles in multiple processes of tumorigenesis. The present study demonstrated that miR-124 was low-expressed in human hepatocellular carcinoma (HCC) tissues and cell lines. In addition, overexpression of miR-124 through infected with miR-124 lentivirus inhibited the proliferation and migration of HCC in vitro and tumorigenesis in vivo, whereas inhibition of miR-124 expression can reverse the process. Moreover, Baculoviral IAP Repeat Containing 3 (BIRC3) was identified as a target gene of miR-124. The BIRC3 mRNA expression was increased in HCC tissues and negatively correlated with miR-124 expression. Knockdown of BIRC3 recovered the miR-124-induced inhibiting effect on HCC progression. Furthermore, we found that up-regulation of miR-124 significantly inhibited p-P65, p-IκBα and c-Myc proteins expression. However, the effect of miR-124 up-regulation on HCC development was partly reversed by BIRC3 restoration. In conclusion, our data proved that miR-124 inhibits the proliferation and migration of HCC at least partly through targeting BIRC3 and regulating NF-κB signaling pathway, and it may be a therapeutic target for HCC prognosis.

MicroRNA‐124: An emerging therapeutic target in cancer

“…Another HCC‐related study demonstrated that miR‐124 could further inhibit the proliferation of HCC cells (SMMC‐7721) by regulating Baculoviral IAP Repeat Containing 3 (BIRC3) and controlling the NF‐kB pathway and migration. The author also pointed out that miR‐124 was a therapeutic target for the prognosis of HCC . Other scholars have also pointed out that in two liver cancer cell lines (SMMC‐7721 and BEL‐7404), miR‐124 could regulate Sp1 expression and inhibit cell migration and invasion .…”

“…The author also pointed out that miR-124 was a therapeutic target for the prognosis of HCC. 44 Other scholars have also pointed out that in two liver cancer cell lines (SMMC-7721 and BEL-7404), miR-124 could regulate Sp1 expression and inhibit cell migration and invasion. 45 Lu et al further confirmed that miR-124 suppressed HepG-2 cell proliferation by reducing STAT3 protein expression levels, and overexpressed miR-124 could significantly promote HCC apoptosis.…”

MicroRNA‑124 negatively regulates chloride intracellular channel�1 to suppress the migration and invasion of liver cancer cells

“…miR-124 is highly expressed in the brain and was previously demonstrated to be a ‘brain-enriched’ miRNA (10,11). In recent years, researchers have demonstrated that the expression of miR-124 is dysregulated in almost all tumors, such as colorectal cancer (27), gastric cancer (28), lung cancer (16) and hepatocellular carcinoma (29). In the progression of cancer, miR-124 not only acts as a suppressor of tumor growth but also decreases cell invasion and metastasis.…”

Chronic Regulation of miR-124-3p in the Perilesional Cortex after Experimental and Human TBI

“…Further, several studies indicate that targets of miR-124-3p promote cellular proliferation and migration in several cancers, including hepatocellular carcinoma [74,75], oral squamous cell carcinomas [76], and gastric cancer [77]. Moreover, in vitro studies demonstrated that transfection of premiR-124-3p in hepatocellular carcinoma cells induces apoptosis and limits proliferation [78,79]. Whether or not the apoptosis is triggered by pushing the non-neuronal cells toward a neuronal identity requires further clarification.…”