Silencing of lncRNA CRNDE attenuates nonsmall‐cell lung cancer progression by mediating the miR‐455‐3p/HDAC2 axis

Abstract

Nonsmall‐cell lung carcinoma (NSCLC) is one of the deadliest malignancies in the world. LncRNAs are confirmed to be involved in the progression of NSCLC. Meanwhile, lncRNA CRNDE is known to be upregulated in NSCLC; however, the mechanism by which CRNDE regulates the tumourigenesis of NSCLC remains unclear. To test the function of CRNDE in NSCLC, cell proliferation, invasion, and migration were investigated by colony formation and Transwell assays, respectively. qPCR and Western blotting were applied to test gene and protein levels. In addition, the relationship among CRNDE, miR‐455‐3p, and HDAC2 was explored by dual‐luciferase and RIP assays. The data revealed that the expression of CRNDE was upregulated in NSCLC tissues, while miR‐455‐3p was downregulated. CRNDE knockdown inhibited the viability, migration and invasion of NSCLC cells or epidermal growth factor receptor gene (EGFR)‐mutant NSCLC cells. Moreover, inhibition of miR‐455‐3p exhibited the opposite effect. CRNDE bound with miR‐455‐3p, and HDAC2 was found to be targeted by miR‐455‐3p. Meanwhile, miR‐455‐3p downregulation reversed the effect of CRNDE knockdown on NSCLC cell function. Furthermore, miR‐455‐3p notably inhibited the growth and invasion of NSCLC cells via downregulation of HDAC2. Knockdown of CRNDE attenuated NSCLC progression via modulation of the miR‐455‐3p/HDAC2 axis. Thus, those findings might provide a novel strategy against NSCLC.

HDAC2 as a target for developing anti-cancer drugs

“…This implies the role of HDAC2 as a downstream effector of EGFR signaling. The expression of an oncogenic long non-coding RNA (CRNDE) was upregulated in NSCLC tissue, whereas miR-455–3p was downregulated [83] . The downregulation of CRNDE inhibited lung cancer progression and decreased the migration and invasion of NSCLC cells by decreasing the expression of miR-455–3p, which targeted HDAC2 [83] .…”

“…The expression of an oncogenic long non-coding RNA (CRNDE) was upregulated in NSCLC tissue, whereas miR-455–3p was downregulated [83] . The downregulation of CRNDE inhibited lung cancer progression and decreased the migration and invasion of NSCLC cells by decreasing the expression of miR-455–3p, which targeted HDAC2 [83] . miR-455–3p expression was downregulated in HCC tissues compared to adjacent normal tissues, and miR-455–3p inhibited cell proliferation but promoted apoptosis in HCC cell lines by decreasing the expression of HDAC2 [84] .…”

“… miRNAs Expression in Cancers Functions/Mechanisms Ref. miR-31 ↓ Hepatocellular carcinoma ↓ Gastric cancer •Targets HDAC2 •Apoptosis [78] , [79] miR-122-5p ↓ Hepatic stellate cells •c-Abl/HDAC2 pathway [80] miR-145 ↓ Hepatocellular carcinoma •Targets HDAC2 •Suppression of tumor growth [81] miR-155 ↓ Breast cancer •Targets HDAC2 •↓ErbB2 signaling [82] miR-455-3p ↓ Hepatic cancer •Targets HDAC2 •↑P53 signaling [83] , [84] miR-490-3p ↓ Prostate cancer •Targets HDAC2 •Suppression of cell proliferation [85] miR-500a-5p ↓ Colorectal cancer •Targets HDAC2 •Suppresses p300/YY1/HDAC2 axis [86] miR-646 ↓ Colorectal cancer •Targets HDAC2 •Suppression of cell proliferation [87] miR-125 ↓ Neuroblastoma •Targeted by HDAC2 •Induces apoptosis [88] miR-503-5p ↓ Esophageal squamous cell carcinoma •Targeted by HDAC2 •Suppression of cell proliferation [90] miR-155 ↓ Hepatic cancer •Targeted by BRCA1-HDAC2 complex [91] miR-183 ↓ Neuroblastoma •Targeted by MYCN-HDAC2 complex [92] miR-200a/-141 ↓ Breast cancer •Targeted by PELP1-HDAC2 complex [93] ↓denotes decreased expression or activity. ↑denotes increased...…”