M6A-Related Long Non-Coding RNA Displays Utility in Predicting Prognosis, Portraying the Tumor Immune Microenvironment and Guiding Immunotherapy in Pancreatic Ductal Adenocarcinoma

Abstract

N6-methyladenosine (m6A) lncRNA plays a pivotal role in cancer. However, little is known about its role in pancreatic ductal adenocarcinoma (PDAC) and its tumor immune microenvironment (TIME). Based on The Cancer Genome Atlas (TCGA) cohort, m6A-related lncRNAs (m6A-lncRNA) with prognostic value were filtered using Pearson analysis and univariate Cox regression analysis. Distinct m6A-lncRNA subtypes were divided using unsupervised consensus clustering. Least absolute shrinkage and selection operator (LASSO) Cox regression was applied to establish an m6A-lncRNA-based risk score signature. The CIBERSORT and ESTIMATE algorithms were employed to analyze the TIME. The expression pattern of TRAF3IP2-AS1 was examined using qRT-PCR. The influence of TRAF3IP2-AS1 knockdown on cell proliferation was estimated by performing CCK8, EdU and colony-formation assays. Flow cytometry was applied to measure the effect of TRAF3IP2-AS1 knockdown on cell cycle and apoptosis. The in vivo anti-tumor effect of TRAF3IP2-AS1 was validated in a tumor-bearing mouse model. Two m6A-lncRNA subtypes with different TIME features were clarified. A risk score signature was constructed as a prognostic predictor based on m6A-lncRNAs. The risk score also correlated with TIME characterization, which facilitated immunotherapy. Finally, the m6A-lncRNA TRAF3IP2-AS1 was proved to be a tumor suppressor in PDAC. We comprehensively demonstrated m6A-lncRNAs to be useful tools for prognosis prediction, TIME depiction and immunotherapeutic guidance in PDAC.

The Effect of Grape Seed Extract on the Alveolar, Jaw, and Skeletal Bone Remodeling: A Scoping Review

“…53 Sox6 is the major factor for healing because it is able to enhance proliferation, inhibit apoptosis, and regulate osteogenesis-related gene expression. 73 The sox family, Sox5, Sox6, and Sox9, is involved in the activation and maintenance of chondrogenesis during fracture healing and the enhancement of chondrogenesis by BMP-2 74 further Sox6 expression also determined bone mineral density. 75 The other protein that influences bone remodeling is Runt-related transcription factor 2 (Runx2).…”

Liquid biopsy techniques and pancreatic cancer: diagnosis, monitoring, and evaluation

“…This is primarily due to the untapped potential of these molecules as PDAC biomarkers, particularly in the case of circRNAs, which is still in its early stages of research [ 188 ]. Most studies on lncRNAs and circRNAs have predominantly focused on their roles as therapeutic targets and prognostic markers for PDAC [ 189 – 192 ]. These studies have provided insights into the involvement of lncRNAs and circRNAs in the initiation and progression of PDAC, suggesting their potential as future diagnostic markers.…”

“…In previous studies, several reports have confirmed the predictive role of ncRNAs in PC. Most of these studies constructed multifactor prognostic risk models and performed survival analyses with these models [ 189 , 229 , 230 ]. Kandimalla and colleagues [ 231 ] developed a risk model for PDAC that includes nine miRNAs (miR-192-5p, 194-5p, 194-3p, 215-5p, 375-3p, 552-3p, and 1251-5p).…”