MicroRNA-183 promotes proliferation and invasion in oesophageal squamous cell carcinoma by targeting programmed cell death 4

Abstract

Background:Dysregulated microRNAs (miRNAs) can serve as oncogenes or suppressors and are associated with many cancers, including oesophageal squamous cell carcinoma (ESCC).Methods:An alignment miRNA array was used to identify differentially expressed miRNAs in ESCC tissues. The expression of miR-183 and programmed cell death 4 (PDCD4) in oesophageal tissues from ESCC and early oesophageal carcinoma patients was examined by quantitative reverse transcriptase PCR and western blotting. A luciferase assay was performed to confirm miR-183 target genes. The effects of miR-183 on ESCC cells and the associated mechanisms were established by in vitro experiments.Results:We identified 51 upregulated miRNAs and 17 downregulated miRNAs in our array, and miR-183 was one of the most upregulated miRNAs. An inverse correlation between miR-183 and PDCD4 levels was found in ESCC tissues. Upregulated expression of miR-183 was not correlated with tumour stage or lymphatic metastasis in ESCC patients. The luciferase assay confirmed that miR-183 directly interacted with the PDCD4 mRNA 3′-untranslated region in ESCC cells. Overexpression of miR-183 led to decreased PDCD4 protein levels and promoted ESCC cell proliferation and invasion. Inhibition of the PI3K/Akt signalling pathway increased PDCD4 protein levels and decreased miR-183 expression in ESCC cells.Conclusions:MiR-183 promotes ESCC cell proliferation and invasion by directly targeting PDCD4, which suggests that it is involved in the pathogenesis of ESCC.

Clinical value and potential pathways of miR-183-5p in bladder cancer: A study based on miRNA-seq data and bioinformatics analysis

“…A remarkably high expression of miR-183-5p that could promote the proliferation and restrain apoptosis in cells through targeting PDCD4 was reported in human breast cancer tissues compared with that in the adjacent noncancerous tissues (20). A similar phenomenon and function of miR-183-5p was also reported in esophageal squamous cell carcinoma and glioblastoma multiforme (21)(22)(23). Upregulation of oncogenic miR-183-5p was reported to enhance the ability of proliferation and metastasis in human pancreatic adenocarcinoma cells probably via targeting the SOCS-6 gene (24).…”

“…miR-183-5p was conformed to affect the biological behavior of cells by targeting different kind of proteins in various types of cancers, such as regulating cell proliferation by targeting PDCD4 in breast (44) and esophageal cancer (21), and esophageal squamous cell carcinoma (22), inhibiting tumorigenesis by targeting MTA1 in nasopharyngeal carcinoma (37), promoting cell proliferation by targeting NEFL in glioblastoma multiforme (45), and suppressing retinoblastoma cell growth by targeting LRP6 (46). However, no study has reported the possible molecular mechanisms of miR-183-5p in BC.…”

“…The abnormally expressed and genetically altered miRNAs have been reported to be involved in the Clinical value and potential pathways of miR-183-5p in bladder cancer: A study based on miRNA-seq data and bioinformatics analysis biological process of BC, including miR-199a-5p, miR-1-3p, miR-9, miR-182 and miR-200b (17)(18)(19). miR-183-5p, located on chromosome 7q32.2, has been studied in various types of cancers, such as human breast cancer (20), esophageal squamous cell carcinoma (21), esophageal squamous cell carcinoma (22), gastric cancer (23), human pancreatic adenocarcinoma (24) and melanoma (25). The expression of miR-183 in BC patients was higher in tissues (26)(27)(28) and serum (29) and showed a moderate value of the BC diagnosis (27).…”

Dysregulation and functional roles of miR-183-96-182 cluster in cancer cell proliferation, invasion and metastasis

“…Previous studies have revealed that miR-183 and miR-182 promote cell proliferation, tumor invasion, and chemo-resistance by inhibition of programmed cell death 4 (PDCD4) in various cancer cells [55, 56, 76–81]. As a typical tumor suppressor gene (TSG), PDCD4 can inhibit eukaryotic translation initiation factor 4A1 (EIF4A1) and NF-κB-dependent transcriptional factors via direct interaction with p65, to induce apoptosis in glioblastoma cells [82].…”

“…miR-183 promotes tumor invasion and metastasis by targeting PDCD4, protein phosphatase 2A (PP2A), EGR1 and PTEN [76, 78, 104, 105]. In addition, TGF-β and Smad can also promote prostate cancer bone metastasis by induction of miR-96 and activation of the mTOR pathway [106].…”