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长链非编码 RNA-p21 通过抑制谷氨酰胺酶的表达抑制谷氨酰胺分解代谢和膀胱癌细胞生长。

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

机构信息

Department of Urology, Shenzhen Second People's Hospital, Clinical Medicine College of Anhui Medical University, Shenzhen 518035, China.

Graduate School, Anhui Medical University, Hefei 230032, China.

出版信息

Biosci Rep. 2019 Apr 12;39(4). doi: 10.1042/BSR20182372. Print 2019 Apr 30.

DOI:10.1042/BSR20182372
PMID:30902882
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6465205/
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.

摘要

长链非编码 RNA p21（lincRNA-p21）在一些实体瘤中下调。谷氨酰胺分解代谢在癌症发展中起着重要作用。然而，在膀胱癌（BC）中，lincRNA-p21 的作用及其与谷氨酰胺分解代谢的关系尚不清楚。在本研究中，我们研究了 lincRNA-p21 和谷氨酰胺分解代谢在 BC 细胞生长中的作用，发现异位 linRNA-p21 表达降低了 BIU87 和 5637 细胞的增殖和生长。在 lincRNA-p21 沉默的 J82 和 T24 细胞中观察到相反的结果。谷氨酰胺酶（GLS）的表达、细胞内谷氨酸和α-酮戊二酸（α-KG）水平受到 lincRNA-p21 的负调控。GLS 过表达逆转了 lincRNA-p21 对 BC 细胞生长和增殖的抑制作用。相反，siRNA 降低 GLS 表达削弱了 lincRNA-p21 低表达 BC 细胞的活力。此外，lincRNA-p21 和 GLS 的丰度决定了 BC 细胞对双-2-（5-苯乙酰胺基-1,2,4-噻二唑-2-基）乙硫醚（BPTES）治疗的敏感性。重要的是，与正常组织相比，BC 组织中 lincRNA-p21 表达降低和 GLS mRNA 水平升高。我们的研究结果表明，lincRNA-p21 通过抑制 GLS 和谷氨酰胺分解代谢来抑制 BC 细胞的生长。靶向该级联可能是 BC 患者的一种有前途的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00f1/6465205/21cf24a8738c/bsr-39-bsr20182372-g6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00f1/6465205/d7348ab18e39/bsr-39-bsr20182372-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00f1/6465205/69bc2d9e1889/bsr-39-bsr20182372-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00f1/6465205/5537f8200730/bsr-39-bsr20182372-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00f1/6465205/d1f436a8abc7/bsr-39-bsr20182372-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00f1/6465205/6b2ff6f5604c/bsr-39-bsr20182372-g5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00f1/6465205/21cf24a8738c/bsr-39-bsr20182372-g6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00f1/6465205/d7348ab18e39/bsr-39-bsr20182372-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00f1/6465205/69bc2d9e1889/bsr-39-bsr20182372-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00f1/6465205/5537f8200730/bsr-39-bsr20182372-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00f1/6465205/d1f436a8abc7/bsr-39-bsr20182372-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00f1/6465205/6b2ff6f5604c/bsr-39-bsr20182372-g5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00f1/6465205/21cf24a8738c/bsr-39-bsr20182372-g6.jpg

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