Methylation of CALCA and CALCB in Pancreatic Ductal Adenocarcinoma.

Feng Gao,Shirong Huang,Xiangqun Fan,Qicai Liu,Fadian Ding,Wei Lian,Sheng Zhang,Jingwen Wang,Guozhong Liu,Xiaoting Lv,Yujia Guo,Jayeeta Ghose

doi:10.1155/2021/2088345

Abstract

Calcitonin gene-related peptide (CGRP) plays a diverse and intricate role in chronic low-grade inflammation and is closely related to specific cancers. It includes two subtypes, CALCA (αCGRP) and CALCB (βCGRP), of which αCGRP expression accounts for more than 90%. Here, we show that methylation of CALCA and CALCB in pancreatic ductal adenocarcinoma was significantly higher than that in paracancer. Western blot and immunohistochemistry showed that CGRP, p-AKT, and p-CREB in the tumor tissues were lower than those in the paracarcinoma tissues. In vivo, the expressions of p-AKT and p-CREB in the pancreatic tissues of CALCA-KO rats were also lower than those of wild type. Methylation of CALCA and CALCB is increased in pancreatic adenocarcinoma, and under that condition, p-AKT and p-CREB levels were decreased.

Highlights

With the mortality approximately equal to the morbidity [1], pancreatic cancer has become one of the most fatal malignant tumors, among which pancreatic ductal carcinoma accounts for more than 90% [2]
Pyrosequencing showed that methylation of Calcitonin gene-related peptide (CGRP) in pancreatic ductal adenocarcinoma was significantly higher than that in paracancer
Bisulfite Sequencing PCR (BSP) and Methylation-Specific PCR (MSP) showed that the methylation level of CpG islands in the promoter region of CGRP in pancreatic cancer tissues was higher than that in paracancerous, indicating that CGRP hypermethylation plays an important role in the development of pancreatic cancer

Summary

Introduction

With the mortality approximately equal to the morbidity [1], pancreatic cancer has become one of the most fatal malignant tumors, among which pancreatic ductal carcinoma accounts for more than 90% [2]. DNA methylation is an important epigenetic modification, which can regulate cell proliferation, apoptosis, gene expression, and stability, and is closely related to the tumor [3, 4]. Calcitonin gene-related peptide (CGRP) is a member of the calcitonin family of peptides, which can act as a growth or survival factor for several tumors, including endocrinerelated tumors [5, 6]. There are two types that exist in CGRP: (1) αCGRP: the product of alternative splicing of the calcitonin gene (CT/CALCA) in neurons and whose expression accounts for more than 90% and is involved in regulating the function of various organs and (2) calcitonin generelated peptide beta (CALCB), which has been discovered to form βCGRP, primarily expressed in the enteric sensory system, gut, and inner organs [5,6,7]. CGRP can stagnate the cell cycle in G0/G1 phase and participate in the regulation of tumor growth [8, 9]

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