MicroRNA-3666 inhibits lung cancer cell proliferation, migration, and invasiveness by targeting BPTF

Abstract

A previous study by our group indicted that overexpression of bromodomain PHD-finger transcription factor (BPTF) occurs in lung adenocarcinoma, and is closely associated with advanced clinical stage, higher numbers of metastatic lymph nodes, the occurrence of distant metastasis, low histological grade, and poor prognosis. Down-regulation of BPTF inhibited lung adenocarcinoma cell proliferation and promoted lung adenocarcinoma cell apoptosis. The purpose of this study is to identify valuable microRNAs (miRNAs) that target BPTF to modulate lung adenocarcinoma cell proliferation. In our results, we found that miR-3666 was notably reduced in lung adenocarcinoma tissues and cell lines. Using an miR-3666 mimic, we discovered that cell proliferation, migration, and invasiveness were suppressed by miR-3666 overexpression, but these were all enhanced when the expression of miR-3666 was reduced. Moreover, bioinformatics analysis using the TargetScan database and miRanda software suggested a putative target site in BPTF 3′-UTR. Furthermore, using a luciferase reporter assay, we verified that miR-3666 directly targets the 3′-UTR of BPTF. Using Western blot we discovered that overexpression of miR-3666 negatively regulates the protein expression of BPTF. Finally, we identified that the PI3K–AKT and epilthelial–mesenchymal transition (EMT) signaling pathways were inhibited by miR-3666 overexpression in lung cancer cells. In conclusion, our data indicate that miR-3666 could play an essential role in cell proliferation, migration, and invasiveness by targeting BPTF and partly inhibiting the PI3K–AKT and EMT signaling pathways in human lung cancers.

Downregulation of circular RNA circPVT1 restricts cell growth of hepatocellular carcinoma through downregulation of Sirtuin 7 via microRNA‐3666

“…Our study identified miR‐3666 as a novel miRNA target of circPVT1. Multiple studies have reported that miR‐3666 is a tumour suppressive miRNA in various cancers . Here, we demonstrate that miR‐3666 is also downregulated in HCC tissues and cell lines and its overexpression suppressed the proliferation of HCC cells, confirming a tumour suppressive function of miR‐3666 in HCC.…”

“…Multiple studies have reported that miR-3666 is a tumour suppressive miRNA in various cancers. [35][36][37] Here, we demonstrate that miR-3666 is also downregulated in HCC tissues and cell lines and its overexpression suppressed the proliferation of HCC cells, confirming a tumour suppressive function of miR-3666 in HCC. Moreover, we found that miR-3666 expression was regulated by circPVT1 in HCC cells.…”

Discovery of High-Affinity Inhibitors of the BPTF Bromodomain

“…The optimal compound in this study, DC-BPi-11, is a potent inhibitor of BPTF-BRD (K D = 20.7 nM) and is selective over the other BRD family members screened. In the cell model of MV-4-11 leukemia cells, DC-BPi-11 reduced proliferation, blocked the cell cycle, and induced apoptosis, which is consistent with previous observations in BPTF genetic studies 34. DC-BPi-11 is expected to enable the further deeper investigation of the role of BPTF-BRD in transcriptional regulation through chemicalgenetic dissection.…”

Long noncoding RNA KCNQ1OT1 contributes to tumor growth and activates Wnt/β‑catenin signaling in osteosarcoma by targeting the miR‑3666/KLF7 axis

“…Previously, miR-3666 was proposed as a tumor suppressor in several types of cancer. miR-3666 was shown to suppress cell growth in lung cancer by targeting BPTF (31). miR-3666 was also shown to suppress the expression of SIRT7 to impair the growth of NScLc cells (32).…”