Identification of m6A-Related lncRNA to Predict the Prognosis of Patients with Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. In the past decades, HCC treatment has achieved great progress; however, the overall prognosis remains poor. Therefore, it is the need of the hour to identify new prognostic biomarkers which can advance our understanding related to the underlying molecular mechanism of adverse prognosis and apply them to clinical work in prognosis prediction. In the present study, data of 576 HCC patients and 292 normal control cases from TCGA and ICGC databases were enrolled to our bioinformatic analysis. SNHG1 and SNHG3 were identified as overlapping genes in TCGA and ICGC databases using Pearson correlation analysis and univariate Cox regression analysis. Further, we used the median of the SNHG1 and SNHG3 expression values as the cutoff values to define the HCC patient groups with high or low expression level. The subsequent analysis revealed that abnormal high expression of SNHG1 or SNHG3 affected the immune infiltration patterns and the crosstalk among immune cells. Moreover, high expression of SNHG1 or SNHG3 resulted in drug resistant to AKT inhibitor VII, bexarotene, bicalutamide, dasatinib, erlotinib, and gefitinib. In addition, lower tumor neoantigen burden was observed in high SNHG1 or SNHG3 group. Further, we found significant relation between the aberrant upregulation of SNHG1 and SNHG3 in tumor grade and stage. We established a nomogram to systematically predict the 5- and 8-year overall survival of liver cancer patients with good accuracy. Finally, the in vitro assays suggest that SNHG1 and SNHG3 promote the proliferative, migratory, and invasive abilities of HCC cells.

SNHG1, interacting with SND1, contributes to sorafenib resistance of liver cancer cells by increasing m6A‐mediated SLC7A11 expression and promoting aerobic glycolysis

“…Several bioinformatic studies revealed that Snhg1 was a m6A related lncRNA potentially involved in prognosis of patients with renal clear cell carcinoma and HCC. 3,21 Moreover, a comprehensive pan-cancer analysis of the prognostic and immunological roles of lncRNAs indicated that Snhg1 expression was regulated by the m6A writer METTL3. However, the involvement of Snhg1 in m6Amediated expression of other genes has not been exactly characterized.…”

“…m6A is a very extensive and important RNA modification in human and animal cells, which is refined controlled by three types of m6A related RNA binding proteins, including writers (m6A methyltransferases), erasers (m6A demethylase), and readers (m6A recognition proteins). Several bioinformatic studies revealed that Snhg1 was a m6A related lncRNA potentially involved in prognosis of patients with renal clear cell carcinoma and HCC 3,21 . Moreover, a comprehensive pan‐cancer analysis of the prognostic and immunological roles of lncRNAs indicated that Snhg1 expression was regulated by the m6A writer METTL3.…”

Construction of N-7 methylguanine-related mRNA prognostic model in uterine corpus endometrial carcinoma based on multi-omics data and immune-related analysis

“…Bicalutamide, a first-generation non-steroidal androgen receptor (AR) antagonist, has become a key part of prostate cancer (PCa) treatment by acting directly on the AR 61 . In Hepatocellular carcinoma (HCC), low expression of SNHG1/SNHG3 was more sensitive to bicalutamide 62 . In a lncRNA prognostic risk model of gastric cancer patients, high-risk patients were more sensitive to chemotherapeutic agents such as bicalutamide compared to the low-risk group 63 .…”

LINC00659 Inhibits Hepatocellular Carcinoma Malignant Progression by Blocking Aerobic Glycolysis through FUS Recruitment and SLC10A1 Modulation

“…GABPB1-AS1 is involved in controlling oxidative stress during erastin-induced ferroptosis in HCC cells [ 18 ]. Additionally, Yang et al have stated that SNHG1 and SNHG3 promote the proliferative, migratory, and invasive abilities of HCC cells [ 19 ]. However, there are few studies analyzing the functions of long intergenic non-protein coding RNA 659 (LINC00659) in malignant diseases [ 20 , 21 ], HCC included.…”