Identification of novel key regulatory lncRNAs in gastric adenocarcinoma

Abstract

Background Stomach adenocarcinoma (STAD) is one of the most common and deadly cancers worldwide. Recent evidence has demonstrated that dysregulation of long noncoding RNAs (lncRNA) is associated with different hallmarks of cancer. lncRNAs also were suggested as novel promising biomarkers for cancer diagnosis and prognosis. Despite these previous investigations, the expression pattern, diagnostic role, and hallmark association of lncRNAs in STAD remain unclear. Results In this study, The STAD lncRNA-mRNA network was constructed based on RNAs that differentially expressed among tumor and normal samples and had a strong expression correlation with others. The high degree nodes of the network were associated with overall survival. In addition, we found that the hubs’ regulatory roles have previously been confirmed in different types of cancers by literature. For example, the HCG22 hub inhibited cell proliferation and invasion and induced apoptosis in oral squamous cell carcinoma (OSCC) cells. The levels of PCNA, Vimentin, and Bcl2 were decreased and E-cadherin and Bax expression was elevated in OSCC cells after HCG22 overexpression. Additionally, HCG22 overexpression inhibited the Akt, mTOR, and Wnt/β-catenin pathways. Then lncRNAs were mapped to their related GO terms and cancer hallmarks. Based on these mappings, we predict the hallmarks that might be associated with each lncRNA. Finally, the literature review confirmed our prediction. Among the 20 lncRNAs of the STAD network, 11 lncRNAs (LINC02560, SOX21-AS1, C5orf66-AS1, HCG22, PGM5-AS1, NALT1, ENSG00000241224.2, TINCR, MIR205HG, HNF4A-AS1, ENSG00000262756) demonstrated expression correlation with overall survival (OS). Based on expression analysis, survival analysis, hallmark associations, and literature review, LINC02560, SOX21-AS1, C5orf66-AS1, HCG22, PGM5-AS1, NALT1, ENSG00000241224.2, TINCR, MIR205HG, HNF4A-AS1 plays a regulatory role in STAD. For example, our prediction of association between C5orf66-AS1 expression dysregulation and “sustaining proliferative signal” and “Activating invasion and metastasis” has been confirmed in STAD, OSCC and cervical cancer. Finally, we developed a lncRNA signature with SOX21-AS1 and LINC02560, which classified patients into high and low-risk subgroups with significantly different survival outcomes. The mortality rate of the high-risk patients was significantly higher compared to the low-risk patients (28/1% vs 60.13). Conclusion These findings help in designing more precise and detailed experimental studies to find STAD biomarkers and therapeutic targets.

LncRNA NALT1 promotes colorectal cancer progression via targeting PEG10 by sponging microRNA-574-5p

“…Furthermore, the vital function and mechanism of lncRNAs in tumorigenesis and progression have been recognized with the help of clinical bioinformatics analysis combined with functional research. Previous studies had identified the oncogenic role of NALT1 in GC tissues and related to poor patients’ prognosis [ 4 , 5 ]. Very little information is available about the molecular mechanisms of NALT1 in CRC carcinogenesis.…”

“…had identified the oncogenic role of NALT1 GC tissues and related to poor patients' prognosis [4,5]. Very little information is available about the molecular mechanisms of NALT1 in CRC carcinogenesis.…”

“…LncRNA NOTCH1 associated lncRNA in T cell acute lymphoblastic leukemia 1 (NALT1) acts as a regulator to be implicated in the development of gastric cancer (GC) [4]. Additionally, dysregulated NALT1 expression was found to be associated with overall survival (OS) in stomach adenocarcinoma (STAD) and might facilitate cancer cell proliferation [5]. Dysregulation of lncRNAs has been commonly found in CRC, which may be involved in CRC cell growth, migration, and metastasis [6][7][8].…”

LncRNA NALT1 promotes colorectal cancer progression via targeting PEG10 by sponging microRNA-574-5p

“…Furthermore, the vital function and mechanism of lncRNAs in tumorigenesis and progression have been recognized with the help of clinical bioinformatics analysis combined with functional research. Previous studies had identi ed the oncogenic role of NALT1 in GC tissues and related with poor patients' prognosis 4,5 . Very little information is available about the molecular mechanisms of NALT1 in CRC carcinogenesis.…”

“…LncRNA NOTCH1 associated lncRNA in T cell acute lymphoblastic leukemia 1 (NALT1) acts as a regulator to be implicated in the development of gastric cancer (GC) 4 . Additionally, dysregulated NALT1 expression was found to be associated with overall survival (OS) in stomach adenocarcinoma (STAD) and might facilitate cancer cell proliferation 5 . Dysregulaton of lncRNAs has been commonly found in CRC, which may be involved in CRC cell growth, migration, and metastasis 6,7,8 .…”