miR-183 inhibits TGF-β1-induced apoptosis by downregulation of PDCD4 expression in human hepatocellular carcinoma cells

Abstract

BackgroundIn recent years, some miRNAs have been reported to be connected closely with the development of human hepatocellular carcinoma. In our previous studies, a set of miRNAs were revealed to be dysregulated in HCC tissues. However, the functions of these miRNAs in HCC remain largely undefined.MethodsThe expression profiles of miR-183 were compared between HCC tissues and adjacent normal liver tissues using qRT-PCR method. This method was used to screen the potential target genes of miR-183. A luciferase reporter assay was conducted to confirm target association. Finally, the functional effect of miR-183 in hepatoma cells was examined.ResultsAmong the 25 HCC samples analyzed, microRNA-183 was significantly up-regulated (twofold to 367-fold) in 17 samples compared with the matching nontumoral liver tissues. Programmed cell death 4 (PDCD4) was identified as the target gene of miR-183. Moreover, PDCD4 is a proapoptotic molecule involved in TGF-β1-induced apoptosis in human HCC cells, we found that miR-183 transfectants were resistant to apoptosis induced by TGF-β1.ConclusionsWe conclude that miR-183 can inhibit apoptosis in human HCC cells by repressing the PDCD4 expression, and miR-183 may play an important role in HCC development.

MicroRNA Profiling of Sporadic and Hereditary Medullary Thyroid Cancer Identifies Predictors of Nodal Metastasis, Prognosis, and Potential Therapeutic Targets

“…These miRNAs have been found to be overexpressed in colorectal cancer (31) and melanoma (32), showing its oncogenic potential in a variety of neoplastic subtypes. Recently Li and colleagues (18) have shown that miR-183 inhibits apoptosis in human hepatocellular cells by repressing the expression of the proapoptotic gene (PDCD4). This miRNA may thus play an important role in the development of hepatocellular carcinoma in humans.…”

“…Differentially expressed miRNAs of proven significance in the literature were selected for validation anaylsis (18)(19)(20)(21)(22). Selected miRNAs were validated in a combined cohort comprising of the original discovery cohort (n ¼ 19) and an external cohort (n ¼ 26) using TaqMan miRNA assays (hsamiR-9*, Assay ID#:002231; hsa-miR-9, Assay ID#: 00583; hsa-miR-183, Assay ID#:002269; hsa-miR-375, Assay ID#:000564; RNU-48, Assay ID#:001006) on the ABI 7900 HT Fast System (Applied Biosystems) following the manufacturer's instructions.…”

“…MiRNA selection for validation was based on the published significance of these miRNAs in other cancers; for example, hepatocellular (18), lung (19), colorectal (20,21), and breast cancer (22). Four differentially expressed miRNAs (miR-183, miR-375, miR-9, and miR-9*) were selected for qPCR validation in both the discovery (n ¼ 19) and external cohorts (n ¼ 26).…”

Primary and Metastatic Tumours of the Liver: Expanding Scope of Morphological and Immunohistochemical Details in the Biopsy

“…MicroRNA-182 could promote metastasis [97]. MicroRNA-183 inhibits apoptosis [98]. MicroRNA expression can be subjected to regulation with IL-6 [25].…”

HBx-induced miR-21 suppresses cell apoptosis in hepatocellular carcinoma by targeting interleukin-12

“…Stem-loop RT-qPCR was performed for miR-21 expression detection as described previously (24), U6 small RNAs were used as an internal control (25). RT-qPCR was carried out using the SuperScript ® III Platinum ® SYBR ® Green One-Step RT-qPCR kit (Thermo Fisher Scientific) according to the manufacturer's instructions.…”