LincRNA-p21 suppresses glutamine catabolism and bladder cancer cell growth through inhibiting glutaminase expression.

Qun Zhou,Yuhan Liu,Yuchen Liu,Hengji Zhan,Weiren Huang,Qunjun Gao,Mengting Ding,Zhiming Cai,Fan Lin,Kang Yang

doi:10.1042/bsr20182372

Abstract

Long intergenic non-coding RNA p21 (lincRNA-p21) is down-regulated in some solid tumors. Glutamine catabolism plays an important role in cancer development. However, the role of lincRNA-p21 and its association with glutamine catabolism remain unknown in bladder cancer (BC). In the present study, we investigated the involvement of lincRNA-p21 and glutamine catabolism in BC cell growth and found that ectopic linRNA-p21 expression reduced the proliferation and growth of BIU87 and 5637 cells. Opposite results were observed in lincRNA-p21 silenced J82 and T24 cells. The expression of glutaminase (GLS), intracellular level of glutamate and α-Ketoglutarate (α-KG) were negatively regulated by lincRNA-p21. GLS overexpression reversed the suppressive function of lincRNA-p21 on BC cell growth and proliferation. In contrast, GLS reduction by siRNA blunted the viability of lincRNA-p21 lowly expressed BC cells. Furthermore, lincRNA-p21 and GLS abundance dictated the sensitivity of BC cells to bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES) treatment. Importantly, reduced lincRNA-p21 expression and increased GLS mRNA level were observed in BC tissues compared with the normal tissues. Our results demonstrate that lincRNA-p21 suppresses the BC cell growth through inhibiting GLS and glutamine catabolism. Targeting this cascade may be a promising treatment strategy for BC patients.

Highlights

Bladder cancer (BC) is one of the most common malignancies, which represents the ninth of all cancer types throughout the world [1]
We investigated the role of lincRNA-p21 and glutamine catabolism in BC cell growth
The function of lincRNA-p21 has been described in other cancers, whereas little is known about its role in BC

Summary

Introduction

Bladder cancer (BC) is one of the most common malignancies, which represents the ninth of all cancer types throughout the world [1]. It caused more than 160000 deaths in 2012 and the lethality has increased these years [2]. The high recurrence rate after standard treatment is the main cause of death, whereas targeted therapies are still lacking for this disease. Long intergenic non-coding RNA p21 (lincRNA-p21) is initially identified as the direct transcriptional target of P53 [4].

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Results

Conclusion