Let-7a inhibits migration, invasion and epithelial-mesenchymal transition by targeting HMGA2 in nasopharyngeal carcinoma

Abstract

BackgroundLet-7a has been shown to play important roles in nasopharyngeal carcinoma (NPC) cell proliferation and apoptosis, but little is known about the function and mechanism of let-7a in nasopharyngeal carcinoma metastasis. We aimed to investigate the function and mechanism of let-7a in nasopharyngeal carcinoma metastasis and clarified the regulation of high mobility group A2 (HMGA2) by let-7a.MethodsThe expression levels of let-7a and HMGA2 were examined in NPC clinical specimens using quantitative reverse transcription-PCR (RT-qPCR). HMGA2 was confirmed as a target of let-7a through luciferase reporter assays, RT-qPCR, and Western blotting. Furthermore, the roles of let-7a and HMGA2 in regulating NPC cells biological properties including proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process were analyzed with let-7a mimics and si-HMGA2 transfected cells.ResultsOur study demonstrated that let-7a was downregulated and inversely associated with the clinical stage, T classification and N classification, and HMGA2 was upregulated and directly associated with the clinical stage and N classification in patients with NPC. Moreover, there was an inverse correlation between let-7a expression and HMGA2 expression in NPC patient. In addition, HMGA2 was negatively regulated at the posttranscriptional level by let-7a via a binding site of HMGA2-3′UTR. In addition, synthetic let-7a mimics suppressed NPC cells migration, invasion and EMT process and knockdown of HMGA2 was consistent with the effects of let-7a in NPC cells.ConclusionLet-7a directly downregulates HMGA2 protein expression, which suppress NPC cell migration, invasion and EMT process. Let-7a could serve as a potential diagnostic marker and therapeutic target for NPC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0462-8) contains supplementary material, which is available to authorized users.

Melanoma cell–derived exosomes promote epithelial–mesenchymal transition in primary melanocytes through paracrine/autocrine signaling in the tumor microenvironment

“…LIN28B and HMGA2 are the two major targets related to EMT, as confirmed by three microRNA databases: TargetScanHuman 7.0 (www.targetscan.org), miRDB (www.mirdb.org), and www.microRNA.org. Let-7, LIN28B, and HMGA2 have been reported to form an axis to adjust the EMT process [13, 14, 32]. In our current study, we also noticed the significant upregulation of LIN28B and HMGA2 after transfection of let-7i mimic followed by co-culturing with A375 or SK-MEL-28 cell-derived exosomes vs controls.…”

“…LIN28B and HMGA2 are the two specific targets of let-7i that are likely to contribute to EMT [13, 14]. We assessed whether let-7i mimic transfection would cause changes in the two target genes and regulate the process of the melanoma cell-derived exosome-mediated EMT.…”

“…Studies also show that miR-23a can regulate EMT through targeting E-cadherin [39, 40]. Let-7a is also involved in cancer cell migration, invasion, and EMT through its specific protein targets, such as LIN28B and HMGA2 [13, 14]. In this current study, even though miR-23a and let-7a showed high-fold changes in serum exosomes isolated from stage I melanoma patients versus non-melanoma subjects, there were no significant differences of miR-23a and let-7a between these two subject groups.…”

MiR-130a-3p inhibits the viability, proliferation, invasion, and cell cycle, and promotes apoptosis of nasopharyngeal carcinoma cells by suppressing BACH2 expression

“…It is widely accepted that EMT process is vital in the invasion as well as metastasis of malignant tumors [41]. Moreover, by simultaneously overexpressing BACH2 and miR-130a-3p in NPC cells, we discovered the regulatory function of this miRNA.…”

CXCR4/Let-7a Axis Regulates Metastasis and Chemoresistance of Pancreatic Cancer Cells Through Targeting HMGA2

“…Recently, let-7a seems to exert its function through regulation of HMGA2 expression in nasopharyngeal carcinoma and esophageal squamous cell carcinoma [29, 30]. By combination of bioinformatic prediction and experimental confirmation, we identified HMGA2 as downstream target of let-7a in PCC and effector in let-7a-induced attenuated cell proliferation, metastasis and drug resistance of PCC.…”