MicroRNA-183-5p contributes to malignant progression through targeting PDCD4 in human hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) remains one of the most common malignant tumors worldwide. This study aimed to investigate the biological role of microRNA-183-5p (miR-183-5p), a novel tumor-related miRNA, in HCC and illuminate the possible molecular mechanisms. The expression patterns of miR-183-5p in clinical samples were characterized using qPCR analysis. Kaplan-Meier survival curve was applied to evaluate the correlation between miR-183-5p expression and overall survival of HCC patients. Effects of miR-183-5p knockdown on HCC cell proliferation, apoptosis, migration and invasion capabilities were determined via CCK8 assays, flow cytometry, scratch wound healing assays and Transwell invasion assays, respectively. Mouse neoplasm transplantation models were established to assess the effects of miR-183-5p knockdown on tumor growth in vivo. Bioinformatics analysis, dual-luciferase reporter assays and rescue assays were performed for mechanistic researches. Results showed that miR-183-5p was highly expressed in tumorous tissues compared with adjacent normal tissues. Elevated miR-183-5p expression correlated with shorter overall survival of HCC patients. Moreover, miR-183-5p knockdown significantly suppressed proliferation, survival, migration and invasion of HCC cells compared with negative control treatment. Consistently, miR-183-5p knockdown restrained tumor growth in vivo. Furthermore, programmed cell death factor 4 (PDCD4) was identified as a direct target of miR-183-5p. Additionally, PDCD4 down-regulation was observed to abrogate the inhibitory effects of miR-183-5p knockdown on malignant phenotypes of HCC cells. Collectively, our data suggest that miR-183-5p may exert an oncogenic role in HCC through directly targeting PDCD4. The current study may offer some new insights for understanding the role of miR-183-5p in HCC.

Clinical values and potential pathways of miR-183-5p in gastric cancer: a study based on integrational bioinformatics analysis

“…MicroRNA (miRNA) is a type of small, non-coding RNA that is involved in post-transcriptional processes and the proliferation, apoptosis, and migration of tumor cells, thus affecting tumorigenesis and the development of tumors (4). The clinicopathological value and potential molecular mechanism of miRNA-183-5p located on chromosome 7q32.2 has been investigated in various cancers, including bladder cancer (5), lung adenocarcinoma (6), hepatocellular carcinoma (7,8), prostate cancer (9), cervical cancer (10), renal cell cancer (11), ovarian cancer (12), and colorectal cancer (13). High expression levels of miR-183-5p displayed correlation with low rates of overall survival, predictive of worse prognoses of patients with various cancers involving…”