MiR-424-5p participates in esophageal squamous cell carcinoma invasion and metastasis via SMAD7 pathway mediated EMT

Abstract

BackgroundsESCC is a life-threatening disease due to invasion and metastasis in the early stage. Great efforts had been made to detect the molecular mechanisms which led to the invasion and metastasis in ESCC. Recent evidence had suggested that deregulation of miR-424-5p took an important role in cancers. However, its role and functional mechanism in ESCC had seldom been elucidated.MethodsThe expression levels of miR-424-5p were detected in ESCC tissues and cell lines by real-time PCR methods. Then, the invasion, metastasis and proliferation ability of ESCC cell lines transfected with miR-424-5p mimics were analyzed separately by transwell invasion assay, wound healing assay and cell proliferation assay. Finally, the target gene of miR-424-5p was studied and verified by luciferase activity assay. And the role of miR-424-5p in EMT was also investigated by real-time PCR and western blot assay.ResultsWe showed that the expression levels of miR-424-5p were decreased both in ESCC tissues and cell lines. Furthermore, the expression levels of miR-424-5p were negatively linked to lymph node metastasis in ESCC tissues. Restoration of miR-424-5p in EC-1 cells by using miR-424-5p mimics could decrease the invasion, metastasis and proliferation of EC-1 cells, indicating its role in inhibition on the invasion and metastasis ability of ESCC cells and tissues. In addition, we demonstrated that SMAD7 was a specific target gene for miR-424-5p by luciferase activity assay and miR-424-5p could not only negatively regulate SMAD7 expression but also participate in EMT via SMAD7, because overexpression of SMAD7 could partly enhance the miR-424-5p anti-EMT function.ConclusionsOur results described that miR-424-5p -SMAD7 pathway contributed to ESCC invasion and metastasis and up-regulation of miR-424-5p perhaps provided a strategy for preventing tumor invasion, metastasis.

Screening key genes and miRNAs in early-stage colon adenocarcinoma by RNA-sequencing

“…30 Mir-424-5p also makes a contribution in preventing the proliferation, migration, and invasion in nonsmall cell lung cancer and esophageal squamous cells. 31,32 Although there is no previous study reporting the association between mir-424-5p and COAD, our study indicated that mir-424-5p is a significantly upregulated miRNA in early-stage COAD. Moreover, mir-424-5p is a regulator of NTRK2, DTNA, PIK3R1, BCL2, and AXIN2 which suggested that mir-424-5p may play a key role in the process of COAD by regulating these DEGs.…”

“…Previous studies have reported that mir-424-5p is a key regulator in various cancers. [30][31][32] Mir-424-5p was indicated to be an anti-oncogene in cervical cancer by blocking cell growth. 30 Mir-424-5p also makes a contribution in preventing the proliferation, migration, and invasion in nonsmall cell lung cancer and esophageal squamous cells.…”

MiR-543 Promotes Migration, Invasion and Epithelial-Mesenchymal Transition of Esophageal Cancer Cells by Targeting Phospholipase A2 Group IVA

“…Recently, it has been revealed that altered expression of miRNA contributes to the invasion and metastasis of many cancers [4,6,18]. Increasing numbers of studies have indicated that among numerous other miRNAs, miR-543 is also involved in the processes of initiation and maintenance of many kinds of cancers, including ESCC [17].…”

“…In this study, the expression level of miR-543 in several ESCC cell lines was determined by qRT-PCR assay, and it was revealed that miR-543 is up-regulated in multiple ESCC cell lines and that it enhances the metastasis of ESCC cells. Many studies have confirmed that miRNAs can regulate the stability and translation of their target mRNAs by attaching to the 3'UTR of the target [6]. In addition, it has been proven that these miRNAs, including miR-21, miR-138, miR-223 and miR-92a, regulate ESCC development through the regulation of the expression of their target genes, such as PTEN (phosphatase and tensin homolog), FBXW7 (F-box and WD repeat domain containing 7) and PDCD4 (programmed cell death 4) [8].…”

“…They upregulate or down-regulate their target genes' expression post-transcriptionally by binding to the 3'-untranslated regions (3'-UTRs) of the mRNAs [6]. Several studies have identified by there are many kinds of miRNAs with variable expression in human tumor tissues [7].…”