The long noncoding RNA TINCR promotes breast cancer cell proliferation and migration by regulating OAS1

Die Lu,Zhihong Zhang,Miaomiao Sun,Shihao Di,Jinhai Tang,Zigui Zou,Linyan Zhou,Shuaishuai Zhuo,Rumeng Bai,Chunni Chen,Tianshi Ma

doi:10.1038/s41420-021-00419-x

Abstract

Breast cancer is the leading cause of cancer-related death in women around the world. It is urgently needed to identify genes associated with tumorigenesis and prognosis, as well as to elucidate the molecular mechanisms underlying the oncogenic process. Long noncoding RNAs (lncRNAs) are widely involved in the pathological and physiological processes of organisms and play an important role as oncogenes or tumor suppressor genes, affecting the development and progression of tumors. In this study, we focused on terminal differentiation-induced non-coding RNA (TINCR) (GeneID:257000) and explore its role in the pathogenesis of breast cancer. The results showed that TINCR was increased in breast cancer tissue, and high expression level of TINCR was associated with older age, larger tumor size, and advanced TNM stage. High level of TINCR can promote proliferation and metastasis of breast cancer cells, while downregulation of TINCR induces G1-G0 arrest and apoptosis. Mechanismly, TINCR can bind to staufen1 (STAU1) and then guide STAU1 (GeneID:6780) to bind to OAS1 mRNA (NM_016816.4) to mediate its stability. Thus low level of OAS1(GeneID:4938) can lead to cell proliferation and migration. This result elucidates a new mechanism for TINCR in breast cancer development and provides a survival indicator and potential therapeutic target for breast cancer patients.

Highlights

Breast cancer is the most common cancer diagnosed among women[1]
The results showed that terminal differentiation-induced non-coding RNA (TINCR) was significantly overexpressed in breast cancer tissues compared to that in adjacent normal tissues (Fig. 1A)
RNA IP revealed significant TINCR enrichment by STAU1 antibody compared with the IgG control (Fig. 5C).We found that after using small interfering RNAs (siRNAs)-STAU1 to knock down the STAU1 level in breast cancer cells, there was no significant change in the expression level of TINCR (Fig. 5D), and there was no significant change in the RNA/ protein level of STAU1 in TINCR knockdown/overexpression cells (Fig. 5E, F), indicating that TINCR can directly bind with STAU1 without influencing its expression level

Summary

Introduction

Breast cancer is the most common cancer diagnosed among women[1]. the treatment of breast cancer has made great progress and the mortality rate has decreased year by year, due to the high incidence of tumor specific death, the prognosis of patients is still worthy of attention[2,3]. TINCR, known as Linc00036 and PLAC2, is a 3.7 kb lncRNA for terminal differentiation induction. It is located on chromosome 19 of the human genome. More and more studies have found that TINCR is abnormally expressed in HCC, lung cancer, bladder cancer, squamous cell carcinoma, breast cancer, prostate cancer, and colorectal cancer, and its expression is closely related to proliferation, apoptosis, invasion, and metastasis, suggesting that TINCR can be used as a biomarker and potential target of treatment[7,12,13,14,15]

Methods

Results

Discussion

Conclusion