ARNTL2 promotes pancreatic ductal adenocarcinoma progression through TGF/BETA pathway and is regulated by miR-26a-5p

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies and the therapeutic outcomes remain undesirable. Increasing evidence shows that aryl hydrocarbon receptor nuclear translocator like 2 (ARNTL2) plays crucial roles in tumorigenesis of multiple tumors. However, the expression status and functions of ARNTL2 in PDAC remain elusive. Here we showed that ARNTL2 expression was markedly upregulated in PDAC tissues and cell lines. elevated expression of ARNTL2 was positively related to unfavorable prognosis. Knockdown of ARNTL2 could suppress motility and invasive ability of PDAC cells in vitro, as well as tumor development in vivo. In addition, microRNA-26a-5p (miR-26a-5p) was identified as the crucial specific arbitrator for ARNTL2 expression and the expression of miR-26a-5p was inversely correlated with ARNTL2 expression in PDAC tissues. Functionally, elevated expression of miR-26a-5p was found to inhibit the proliferation, migration, and invasion of PDAC cells in vitro, while ARNTL2 increased expression could partially abolish the suppressive effect of miR-26a-5p. Mechanism study indicated that elevated expression of miR-26a-5p suppressed TGF/BETA signaling pathway by targeting ARNTL2 in PDAC cells. In conclusion, our data suggested that ARNTL2 acted as an oncogene to regulate PDAC growth. MiR-26a-5p/ARNTL2 axis may be a novel therapeutic candidate target in PDAC treatment.

MicroRNA-26a-5p: multiple functions, multiple possibilities – a mini-review

“…Thanks to this process, tumour growth was inhibited and its invasiveness was reduced. Similar results were obtained in a study on mice with subcutaneous tumour xenografts [6].…”

“…At present, MicroRNA-26a-5p (miR-26a-5p) is a little-known molecule although its participation in both neoplastic and nonneoplastic processes is understood. There are reports of a significant suppressive role of miR-26a-5p in various types of cancer [6]. Due to its function of regulating the expression of proteins in a post-transcriptional manner, miR-26a-5p can be used therapeutically in various neoplasms, including those with poor prognosis.…”

A Combined Two-mRNA Signature Associated With PD-L1 and Tumor Mutational Burden for Prognosis of Lung Adenocarcinoma

“…GO gene sets variation analysis revealed that pathways such as “Myogenesis,” “K-ras Signaling Down,” “Estrogen Response Early” were more active in high-risk patients, while pathways such as “E2F Targets,” “G2M Checkpoint,” and “mTORC1 signaling” were more enriched in low-risk patients. Although the two signature genes in our study were previously shown to identify as potential biomarkers ( Luo et al, 2020 ; Wang et al, 2020 ), differences in metabolic pathways between high- and low-risk patients based on the established signature have not been previously reported in LUAD, indicating that the two signature genes and varied gene sets or pathways in GSVA have the potential to be further investigated. Additionally, some studies ( Budhu et al, 2006 ; Galon et al, 2006 , 2007 ) have proved that all kinds of cells, cytokines and chemokines that interact with tumor cells in the tumor microenvironment, especially immune cells, were increasingly considered to play vital roles in the body’s anti-tumor activities.…”

Upregulation of B3GNT3 Correlates With Poor Prognosis and Decreased Immune Cell Infiltration In Pancreatic Adenocarcinoma

“…Besides, ubiquitination and adheres were related to the B3GNT3 signature. All these biological functions were reported to be vital in the tumorigenesis and progression of PAAD [33][34][35]. Hence, biological analysis revealed B3GNT3 promoting the development of PAAD through multiple pathways.…”