MicroRNA-4458 suppresses the proliferation of human lung cancer cells in vitro by directly targeting Lin28B

Abstract

Previous studies have shown that the expression of microRNA-4458 (miR-4458) is dysregulated in hepatocellular carcinoma and colon cancer. In this study, we investigated the direct target of miR-4458 and its biological functions in human lung cancer cells. By using the database TargetScan, we identified Lin28B, an oncogene, as a direct target gene of miR-4458. In dual-luciferase reporter assay, we found that miR-4458 mimics dose-dependently inhibited the luciferase activity of the wild-type 3'UTR of Lin28B in human lung cancer A549 and NCI-H1299 cell lines without affecting its mutant forms, whereas anti-miR-4458, an inhibitor of miR-4458, dose-dependently promoted the luciferase activity of the wild-type 3'UTR of Lin28B in A549 and NCI-H1299 cell lines without affecting its mutant forms. Overexpression of miR-4458 significantly decreased the protein levels of Lin28B in the cells, and inhibited the cell growth and colony formation. Conversely, knockdown of miR-4458 with anti-miR-4458 significantly increased the protein levels of Lin28B, and promoted the cell proliferation, which could be reverted by knockdown of Lin28B expression. In addition, we detected the expression of Lin28B using RT-PCR in 40 human lung cancer tissues and matched peritumoral tissues, and found that Lin28B was overexpressed in lung cancer tissues and negatively correlated with miR-4458 expression (r=-0.694, P<0.05). We conclude that miR-4458 is a tumor suppressor, and Lin28B is the direct target of miR-4458. These results suggest the modulation of miR-4458/Lin28B expression offers a potential therapeutic strategy for lung cancer.

MiR-490-3p Functions As a Tumor Suppressor by Inhibiting Oncogene VDAC1 Expression in Colorectal Cancer

“…MicroRNA is a type of highly conserved non-coding RNA consisting of 18-25 nucleotides 5 . Previous studies have reported that miRNAs were closely related to the development and progression of cancers, including pancreatic cancer 22 , esophageal squamous cell carcinoma 23 , lung cancer 24 , gastric cancer 25 , colorectal cancer 26 and osteosarcoma 27 . MiR-490-3p is a newly identified microRNA and its biological functions in cancers is attracting more and more attentions 28 .…”

MicroRNA-4458 suppresses migration and epithelial&ndash;mesenchymal transition via targeting HMGA1 in non-small-cell lung cancer cells

“…Previous studies have already found that miRNAs could inhibit the transcription of target mRNAs via binding to complementary 3′-UTR. Emerging evidence indicates that microRNA-4458 (miR-4458) plays an important role in different cell processes, including proliferation, cell cycle, and glycolysis in hepatocellular carcinoma,8 colon cancer,9 and lung cancer 10,11. However, the molecular mechanism of miR-4458 in NSCLC has not been fully understood.…”

Circular RNA PRMT5 confers cisplatin‐resistance via miR‐4458/REV3L axis in non‐small‐cell lung cancer

“…A previous study reported that miR‐4458 was aberrantly expressed in hepatocellular carcinoma (Tang, Sun, Yu, Yang, & Zhu, 2015) and colon cancer (Qin, Cheng, Lu, & Wang, 2016). Specifically, miR‐4458 suppressed tumor growth in human lung cancer cells via targeting lin‐28 homolog B, showing as the repression of cell proliferation (C. H. Liu et al, 2017). EV3‐like DNA‐directed polymerase ζ catalytic subunit (REV3L) that encodes the catalytic subunit of DNA polymerase ζ is responsible for translesional replication, which was closely linked to tumorigenesis and chemoresistance (Kong, Murata, & Digman, 2018).…”