Bioinformatic analyses and experimental validation of the role of m6A RNA methylation regulators in progression and prognosis of adrenocortical carcinoma

Abstract

M6A-related genes have been proven to play an important role in many cancers. However, the role of that in adrenocortical carcinoma (ACC) has not been fully elucidated. In the present study, 77 ACC samples from TCGA database were divided into localized ( n = 46) and metastatic ( n = 31) groups. Three differential expression genes (DEGs) and five prognostic m6A genes were screened out. M6A-related risk signature (RBM15 and HNRNPC) was constructed by the Lasso regression analysis. In TCGA cohort (training cohort), the risk signature was identified as an ACC-independent prognostic factor and can distinguish the prognostic difference of ACC patients with clinical stage I-II, T3-4 and N0 stages. A nomogram combining T stage and m6A risk score was constructed to predict the overall survival rate (OSR) of individual at 1,2,3 year. Meanwhile, its prognostic value was also confirmed in the validation cohort (GSE33371 dataset). The potential associations between m6A risk level and immune checkpoint inhibitors (ICIs) therapy were also investigated via the TISIDB online tool. High m6A risk not only can suppress immunotherapy-related biological processes, but also repress the expressions of immune-checkpoint markers. Moreover, five pairs of clinical specimens were collected to confirm the overexpression of HNRNPC and non-ectopic expression of RBM15 in tumor tissues. HNRNPC was proven to promote the proliferation, migration and invasion of H295R and SW13 cells through MTT and Transwell assays. In conclusion, the m6A-related risk signature was beneficial for prognostic analysis and can affect immune microenvironment in ACC. HNRNPC played a pro-cancer role in ACC progression.

Dorsal Striatum Transcriptome Profile Profound Shift in Repeated Aggression Mouse Model Converged to Networks of 12 Transcription Factors after Fighting Deprivation

“…Overall, the cluster manifests negative regulation of transcription. In particular, Rbm15 is reported to facilitate m6a posttranscriptional methylation of mRNA [ 37 ]. To the best of our knowledge, we are the first to report such DEGs in regard to DS cAMP signaling.…”

Pyroptosis-Related Risk Signature Exhibits Distinct Prognostic, Immune, and Therapeutic Landscapes in Hepatocellular Carcinoma

“…Transwell migration and invasion assays were performed as described in a previous study ( Xu et al, 2021 ). For this assay, 100 μL cell suspensions (2 × 10 4 per well) were placed into 24-well Transwell chambers (Corning, NY, United States).…”

An analysis of the role of HnRNP C dysregulation in cancers

“…It also has multiple other functions, such as increasing differentiation in type II testicular germ cell tumours (TGCTs) [ 72 ], inducing cell death in ovarian cancer, promoting chemotherapy resistance, indicating overall survival (OS) in gastric cancer, and promoting the progression of colorectal cancer. It also showed value in diagnosis, progression and prognosis evaluation in lung adenocarcinoma, oesophageal cancer, adrenocortical carcinoma [ 73 ], urothelial carcinoma of the bladder [ 74 ], and kidney renal papillary cell carcinoma [ 75 – 77 ].…”