LINC00467 Is Upregulated by DNA Copy Number Amplification and Hypomethylation and Shows ceRNA Potential in Lung Adenocarcinoma

Abstract

Lung adenocarcinoma (LUAD) is the most common histological lung cancer, and it is the leading cause of cancer-related deaths worldwide. Long noncoding RNAs (lncRNAs) have been implicated in tumorigenesis. LINC00467 is a novel lncRNA that is abnormally expressed in several cancer types including LUAD. However, its function and regulatory mechanism in LUAD progression remain unclear. In this study, based on The Cancer Genome Atlas data mining, we demonstrated that DNA copy number amplification and hypomethylation was positively correlated with LINC00467 expression in LUAD. In addition, DNA copy number amplification was significantly associated with distant metastasis, immune infiltration and poor survival. Microarray analysis demonstrated that LINC00467 knockdown in the LUAD A549 cell line led to a distinct microRNA expression profile that impacted various target genes involved in multiple biological processes. This finding suggests that LINC00467 may regulate LUAD progression by functioning as a competing endogenous RNA (ceRNA). Finally, we constructed a ceRNA network that included two microRNAs (hsa-miR-1225-5p, hsa-miR-575) and five mRNAs (BARX2, BCL9, KCNK1, KIAA1324, TMEM182) specific to LINC00467 in LUAD. Subsequent Kaplan-Meier survival analysis in both The Cancer Genome Atlas and Gene Expression Omnibus databases revealed that two genes, BARX2 and BCL9, were potential prognostic biomarkers for LUAD patients. In conclusion, our data provide possible mechanisms underlying the abnormal upregulation of LINC00467 as well as a comprehensive view of the LINC00467-mediated ceRNA network in LUAD, thereby highlighting its potential role in diagnosis and therapy.

Drug repositioning in non-small cell lung cancer (NSCLC) using gene co-expression and drug–gene interaction networks analysis

“…"Tandem of pore domain in a weak inwardly rectifying K + channels (TWIK)" pathway involves two genes of the magenta module, including KCNK7 and KCNK1 . Wen Wang and colleagues 114 constructed a ceRNA network, and they concluded that KCNK1 is specific to LINC00467 in Lung adenocarcinoma. The "Tight junction interactions" pathway involves three genes of the magenta module containing PRKCI, CLDN20 , and PARD6G .…”

Long Noncoding RNA LINC00467: Role in Various Human Cancers

“…Through bioinformatic analysis, two potential prognostic biomarkers (BARX2 and BCL9) for LUAD were revealed. ( Wang et al, 2021 ) Based on the results of these reports, LINC00467 stands as a potential diagnostic and prognostic biomarker, as well as a suitable therapeutic target for LUAD.…”

LINC00467: an oncogenic long noncoding RNA

“…RT-qPCR assays were used to measure LINC00467 expression in 35 paired LUAD and adjacent normal lung tissues and researchers revealed that the expression level of LINC00467 in LUAD tissues was increased compared with that in adjacent normal lung tissues [22]. Wang et al [23] analyzed Fig. 1 LINC00467 expression in various cancers online sequencing data from the TCGA LUAD cohort and observed a positive correlation between LINC00467 DNA copy number values and LINC00467 mRNA expression.…”

“…1 LINC00467 expression in various cancers online sequencing data from the TCGA LUAD cohort and observed a positive correlation between LINC00467 DNA copy number values and LINC00467 mRNA expression. Subsequently, they assessed the independent prognostic value of LINC00467 copy number alterations in terms of tumor metastasis and overall survival which predict poor prognosis in LUAD [23].The high expression of LINC00467 promoted the proliferation, migration, stemness, invasion of lung cancer cells and modulated cell cycle arrest and apoptosis [16,[19][20][21][22]24]. These results suggested that LINC00467 played an oncogenic function and performed an important role in LUAD development.…”

“…Ding et al [21] revealed a novel linc00467/miR-20b-5p/CCND1 signaling in LUAD cells, providing efforts into lung cancer therapy. Wang et al [23] constructed a competing endogenous RNA (ceRNA) network specific to LINC00467 in LUAD to regulate cancer progression. In addition, silencing LINC00467 upregulates miR-125a-3p to decrease cisplatin resistance via inhibiting SIRT6 and inactivating the ERK1/2 signaling pathway [24].…”