LncRNA PANDAR regulates the G1/S transition of breast cancer cells by suppressing p16(INK4A) expression.

Yi Sang,Jianjun Tang,Liping Li,Siwei Li,Xiao-Bin Lv,Xia Qian,Liang-Ming Deng,Lijuan Liu,Xiaofeng Tang,Yanqin Luo,Chun Cheng

doi:10.1038/srep22366

Abstract

It has been reported that lncRNA PANDAR (promoter of CDKN1A antisense DNA damage-activated RNA) is induced as a result of DNA damage, and it regulates the reparation of DNA damage. In this study, we investigated the role of lncRNA PANDAR in the progression of breast cancer and found that PANDAR was up-regulated in breast cancer tissues and cell lines. The knockdown of PANDAR suppresses G1/S transition of breast cancer cells. We demonstrated mechanistically that the regulation of G1/S transition by PANDAR was partly due to the transcriptional modulation of p16INK4A. Moreover, we showed that PANDAR impacted p16INK4A expression by regulating the recruitment Bmi1 to p16INK4A promoter. To our knowledge, this is the first study which showed the functional roles and mechanisms of PANDAR in regulating the progression of breast cancer. The PANDAR/Bmi1/p16INK4A axis could serve as novel targets for breast cancer therapy.

Highlights

Noncoding RNAs, such as microRNAs3–8 and lncRNAs9–13, have become a hotspot in the development and progress of breast cancer
It was reported that lncRNAs SSPRY4-IT1 and UCA1 were dysregulated in breast cancer samples and increased the proliferation of breast cancer cells[19,20]
These results indicate that PANDAR was dysregulated in breast cancer

Summary

Introduction

Noncoding RNAs, such as microRNAs3–8 and lncRNAs9–13, have become a hotspot in the development and progress of breast cancer. Increasing evidence have suggested that numerous lncRNAs may play critical roles in breast cancers[11,17,18]. Another study revealed that lncRNA EFNA3 was induced by hypoxia and that it promoted metastatic dissemination of breast cancer[21]. It was reported that lncRNA INXS induced apoptosis of breast cancer cells[22]. Han et al reported that PANDAR was down-regulated in non-small cell lung cancer (NSCLC). Peng et al found that PANDAR was up-regulated in hepatocellular carcinoma and that a low PANDAR level predicted a good prognosis[26]. These reports indicate that PANDAR plays complicated roles in cancers. Our findings suggest that PANDAR could function as a tumor-promoting gene and regulate the cell cycle of breast cancer cells

Methods

Results

Conclusion