LncRNA DGCR5 promotes lung adenocarcinoma (LUAD) progression via inhibiting hsa‐mir‐22‐3p

Abstract

Long non-coding RNAs (lncRNAs) serve critical roles in the pathogenesis of various cancers, including lung adenocarcinoma (LUAD). Herein, in this study, we aimed to investigate the biological and clinical significance of lncRNA DiGeorge syndrome critical region gene 5 (DGCR5) in LUAD. It was observed that DGCR5 was upregulated in LUAD tissues and LUAD cell lines. Inhibition of DGCR5 can prevent LUAD progression via playing anti-apoptosis roles. Both mRNA expression and protein levels of BCL-2 were increased by DGCR5 downregulation while reversely BAX was increased. Additionally, a novel microRNA target of DGCR5, hsa-mir-22-3p was identified through bioinformatics search and confirmed by dual-luciferase reporter system. Gain and loss-of-function studies were performed to verify whether DGCR5 exerts its biological functions through regulating hsa-mir-22-3p in vitro. Overexpression of DGCR5 was able to reverse the tumor inhibitory effect of hsa-mir-22-3p mimics. Furthermore, in vivo tests tumor xenografts were established to detect the function of DGCR5 in LUAD tumorigenesis. Downregulated DGCR5 expression was greatly associated with smaller tumor size, implying a favorable prognosis of LUAD patients. Taken these together, DGCR5 could be considered as a prognostic biomarker and therapeutic target in LUAD diagnosis and treatment.

Long noncoding RNA DGCR5 suppresses gastric cancer progression by acting as a competing endogenous RNA of PTEN and BTG1

“…Amounting evidence reveals that lncRNAs are actively involved in the initiation, progression, metastasis, and chemoresistence of cancers via acting as oncogenes or tumor suppressors (Chandra Gupta & Nandan Tripathi, ; Huarte, ; T. Li et al, ; Sun et al, ). DGCR5 has recently been shown to correlate with a variety of cancers including hepatocellular carcinoma, pancreatic ductal adenocarcinoma, and lung cancer (Chen et al, ; Dong et al, ; R. Huang et al, ; Luo et al, ; R. Wang et al, ; Yong et al, ). Although the specific role of DGCR5 in tumorigensis of different cancers remains controversial especially in lung cancer, the published data generally suggest that DGCR5 functions as a tumor suppressor.…”

“…Emerging evidence supports that DGCR5 plays a pivotal role in the progression of various cancers including hepatocellular carcinoma, pancreatic ductal adenocarcinoma, and lung cancer (Chen, Zhang, Xu, Zhu, & Hu, ; Dong, Wang, Jin, Zeng, & Pan, ; R. Huang et al, ; Luo et al, ; Wang, Dong, Zeng, Pan, & Jin, ; Yong et al, ). Generally, these findings suggest that DGCR5 acts as a tumor suppressor in both hepatocellular carcinoma and pancreatic ductal adenocarcinoma (R. Huang et al, ; Yong et al, ), whereas its role in lung cancer is still on debate so far (Chen et al, ; Dong et al, ; Luo et al, ; R. Wang et al, ). For instance, R. Huang et al () showed that the downregulation of DGCR5 was associated with poor prognosis in hepatocellular carcinoma.…”

Long non‐coding RNAs: How to regulate the metastasis of non–small‐cell lung cancer

“…DGCR5, also known as Linc00037, was a kind of LncRNA involved in lung cancer, Huntington's disease neurodegeneration and hepatocellular carcinoma . Wang et al reported DGCR5 acted as an oncogene and revealed the possible mechanism for an interaction between DGCR and miR‐330‐5p in lung CSCs.…”

Deregulated lncRNA expression profile in the mouse lung adenocarcinomas with KRAS‐G12D mutation and P53 knockout

“…The aberrant expression of lncRNAs can be used as tumour promoters or inhibitors. Studies have indicated that lncRNAs play critical roles in lung cancer development and progression by altering multiple signalling pathways, and some cancer‐associated lncRNAs have been identified, such as H19, MALAT(lung adenocarcinoma associated transcript 1), MIR31HG, HOTAIR, DGCR5, AFAP1‐AS1, SNHG1 and RMRP . However, the research on the identification of additional lung cancer‐associated lncRNAs remains to be investigated.…”