LncRNA ANRIL aggravates the chemoresistance of pancreatic cancer cells to gemcitabine by targeting inhibition of miR-181a and targeting HMGB1-induced autophagy.

Lei Wang,Kun Zhou,Hang Yin,Lei Li,Rongrong Bi

doi:10.18632/aging.203251

Abstract

Recent studies focus on long noncoding RNAs (lncRNA) as crucial regulators of cancer biology that contribute to essential cancer cell functions such as cell proliferation, apoptosis, and metastasis. In pancreatic cancer, several lncRNAs have been mentioned as important actors in tumorigenesis. However, the function of lncRNA ANRIL (named as ANRIL as follows) in pancreatic cancer has not been elucidated. In the present study, we show that ANRIL was up-regulated while miR-181a was down-regulated in pancreatic cancer tissues and HMGB1 was highly expressed. Knockdown of ANRIL in pancreatic cancer repressed cellular proliferation, invasion, migration, and reduced chemotherapy resistance to gemcitabine. ANRIL was negatively correlated with miR-181a, while overexpression of miR-181a could reverse the effect. For further mechanism research, we found that miR-181a aimed to HMGB1 which activated cell autophagy. Taken together, our results implicate that the ANRIL, by targeting miR-181a, activates the HMGB1-induced cell autophagy, which is thought to be critical for oncogenesis.

Highlights

Pancreatic cancer (PC) as a kind of common and frequent malignancy across the world, which may the major causes of cancer mortality in developed countries [1, 2]
The results of Quantitative real-time PCR (qRT-PCR) and western blot showed that the expression of ANRIL and HMGB1 was obviously higher in pancreatic cancer tissues than that in adjacent tissues (Figure 1A)
Contrary to its above results, miR-181a was significantly lower in both pancreatic cancer tissues and cell lines (Figure 1C), which indicate that miR-181a may be regulated by ANRIL, which promotes the expression of HMGB1

Summary

Introduction

Pancreatic cancer (PC) as a kind of common and frequent malignancy across the world, which may the major causes of cancer mortality in developed countries [1, 2]. Pancreatic cancer is still a destructive malignant disease the progress development of surgical techniques and adjuvant drugs. The morbidity of pancreatic cancer in China is lower compared with western countries, but it has increased high in recent years. It has been reported that there are about 34509 men and 23226 women that die in pancreatic cancer, and the number of deaths exceeded that of the United States [3]. This malignant tumor tends to be in late stage after definite diagnosis due to progress rapidly [4]. It is better to learn the mechanism of PC and identify the innovative biological targets

Methods

Results

Conclusion