MiR-135b-5p is an oncogene in pancreatic cancer to regulate GPRC5A expression by targeting transcription factor KLF4

Jinhong Wu,Yun Jin,Huanbing Zhu,Dan Ye,Daren Liu

doi:10.1038/s41420-022-00814-y

Abstract

KLF4 is implicated in tumor progression of pancreatic cancer, but the molecular regulatory mechanism of KLF4 needs to be further specified. We aimed to probe molecular regulatory mechanism of KLF4 in malignant progression of pancreatic cancer. qRT-PCR or western blot was completed to test levels of predicted genes. Dual-luciferase and chromatin immunoprecipitation (ChIP) assays were designed to validate binding between genes. Cell viability and oncogenicity detection were used for in vitro and vivo functional assessment. KLF4 was a downstream target of miR-135b-5p. KLF4 could regulate GPRC5A level. MiR-135b-5p was notably increased in cancer cells, and overexpressing KLF4 functioned a tumor repressive role, which could be restored by miR-135b-5p. Besides, cell malignant phenotypes could be inhibited through reducing miR-135b-5p level, but they were restored by GPRC5A. Our results stressed that KLF4, as a vital target of miR-135b-5p, could influence promoter region of GPRC5A, thus affecting the malignant progression of pancreatic cancer.

Highlights

Pancreatic cancer, a highly malignant disease of digestive tract, is known as “the king of cancer” due to its latency, difficulty in early diagnosis, low surgical resection rate, low sensitivity to radiotherapy and chemotherapy, high aggressiveness, high risk of relapse, and poor prognosis [1, 2]
Binding property of level could slow down cell growth of pancreatic cancer in vivo, mutant GPRC5A promoter with KLF4 noticeably weakened
Results suggested that transcription factor KLF4 could bind to

Summary

Introduction

Pancreatic cancer, a highly malignant disease of digestive tract, is known as “the king of cancer” due to its latency, difficulty in early diagnosis, low surgical resection rate, low sensitivity to radiotherapy and chemotherapy, high aggressiveness, high risk of relapse, and poor prognosis [1, 2]. More and more studies disclosed that miRNAs are tightly related to migration and invasion of pancreatic cancer cells and are abnormally expressed in tumor tissue and cell line. MiR-939-5p serves as a novel modulator of ARHGAP4 to affect the proliferation and migration of pancreatic cancer [8]. The abnormity in miR-135b5p expression is implicated with unfavorable clinical features or prognoses in pancreatic cancer patients [9]. Either the mechanism whereby miR-135b-5p regulates pancreatic cancer or target genes of miR-135b-5p are underexplored

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Conclusion