LAMTOR5-AS1 Regulates Chemotherapy-induced Oxidative Stress by Controlling the Expression Level and Transcriptional Activity of NRF2 in Osteosarcoma Cells

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2021 Dec 4

PMID 34862368

Citations 17

Authors

Youguang Pu

Yiao Tan

Chunbao Zang

Fangfang Zhao

Cifeng Cai

Lingsuo Kong

Hui Deng

Fengmei Chao

Ran Xia

Minghua Xie

Fangfang Ge

Yueyin Pan

Shanbao Cai

Dabing Huang

Affiliations

Soon will be listed here.

Abstract

Long-noncoding RNAs (lncRNAs) play roles in regulating cellular functions. High-throughput sequencing analysis identified a new lncRNA, termed LAMTOR5-AS1, the expression of which was much higher in the chemosensitive osteosarcoma (OS) cell line G-292 than in the chemoresistant cell line SJSA-1. Further investigations revealed that LAMTOR5-AS1 significantly inhibits the proliferation and multidrug resistance of OS cells. In vitro assays demonstrated that LAMTOR5-AS1 mediates the interaction between nuclear factor erythroid 2-related factor 2 (NFE2L2, NRF2) and kelch-like ECH-associated protein 1 (KEAP1), which regulate the oxidative stress. Further mechanistic studies revealed that LAMTOR5-AS1 inhibited the ubiquitination degradation pathway of NRF2, resulting in a higher level of NRF2 but a loss of NRF2 transcriptional activity. High level of NRF2 in return upregulated the downstream gene heme oxygenase 1 (HO-1). Moreover, NRF2 controls its own activity by promoting LAMTOR5-AS1 expression, whereas the feedback regulation is weakened in drug-resistant cells due to high antioxidant activity. Overall, we propose that LAMTOR5-AS1 globally regulates chemotherapy-induced cellular oxidative stress by controlling the expression and activity of NRF2.

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References

Rogozhin D, Bulycheva I, Konovalov D, Talalaev A, Roshchin V, Ektova A . [Classical osteosarcoma in children and adolescent]. Arkh Patol. 2016; 77(5):68-74. DOI: 10.17116/patol201577568-74. View

Mirabello L, Troisi R, Savage S . Osteosarcoma incidence and survival rates from 1973 to 2004: data from the Surveillance, Epidemiology, and End Results Program. Cancer. 2009; 115(7):1531-43. PMC: 2813207. DOI: 10.1002/cncr.24121. View

Chou A, Gorlick R . Chemotherapy resistance in osteosarcoma: current challenges and future directions. Expert Rev Anticancer Ther. 2006; 6(7):1075-85. DOI: 10.1586/14737140.6.7.1075. View

Ferrari S, Serra M . An update on chemotherapy for osteosarcoma. Expert Opin Pharmacother. 2015; 16(18):2727-36. DOI: 10.1517/14656566.2015.1102226. View

He H, Ni J, Huang J . Molecular mechanisms of chemoresistance in osteosarcoma (Review). Oncol Lett. 2014; 7(5):1352-1362. PMC: 3997672. DOI: 10.3892/ol.2014.1935. View

Song B, Wang Y, Xi Y, Kudo K, Bruheim S, Botchkina G . Mechanism of chemoresistance mediated by miR-140 in human osteosarcoma and colon cancer cells. Oncogene. 2009; 28(46):4065-74. PMC: 2783211. DOI: 10.1038/onc.2009.274. View

Gomes C, Welling M, Que I, Henriquez N, van der Pluijm G, Romeo S . Functional imaging of multidrug resistance in an orthotopic model of osteosarcoma using 99mTc-sestamibi. Eur J Nucl Med Mol Imaging. 2007; 34(11):1793-803. DOI: 10.1007/s00259-007-0480-8. View

Engreitz J, Ollikainen N, Guttman M . Long non-coding RNAs: spatial amplifiers that control nuclear structure and gene expression. Nat Rev Mol Cell Biol. 2016; 17(12):756-770. DOI: 10.1038/nrm.2016.126. View

Wang Y, Zeng X, Wang N, Zhao W, Zhang X, Teng S . Long noncoding RNA DANCR, working as a competitive endogenous RNA, promotes ROCK1-mediated proliferation and metastasis via decoying of miR-335-5p and miR-1972 in osteosarcoma. Mol Cancer. 2018; 17(1):89. PMC: 5948795. DOI: 10.1186/s12943-018-0837-6. View

10.

Han J, Shen X . Long noncoding RNAs in osteosarcoma via various signaling pathways. J Clin Lab Anal. 2020; 34(6):e23317. PMC: 7307344. DOI: 10.1002/jcla.23317. View

11.

Wang Y, Xu Z, Wang X, Zheng J, Du Q, Yang J . LncRNA FOXC2-AS1 regulated proliferation and apoptosis of vascular smooth muscle cell through targeting miR-1253/FOXF1 axis in atherosclerosis. Eur Rev Med Pharmacol Sci. 2020; 24(6):3302-3314. DOI: 10.26355/eurrev_202003_20698. View

12.

Mittler R . ROS Are Good. Trends Plant Sci. 2016; 22(1):11-19. DOI: 10.1016/j.tplants.2016.08.002. View

13.

Finkel T, Holbrook N . Oxidants, oxidative stress and the biology of ageing. Nature. 2000; 408(6809):239-47. DOI: 10.1038/35041687. View

14.

Wang J, Yi J . Cancer cell killing via ROS: to increase or decrease, that is the question. Cancer Biol Ther. 2008; 7(12):1875-84. DOI: 10.4161/cbt.7.12.7067. View

15.

Panieri E, Santoro M . ROS homeostasis and metabolism: a dangerous liason in cancer cells. Cell Death Dis. 2016; 7(6):e2253. PMC: 5143371. DOI: 10.1038/cddis.2016.105. View

16.

He L, Lai H, Chen T . Dual-function nanosystem for synergetic cancer chemo-/radiotherapy through ROS-mediated signaling pathways. Biomaterials. 2015; 51:30-42. DOI: 10.1016/j.biomaterials.2015.01.063. View

17.

Pelicano H, Carney D, Huang P . ROS stress in cancer cells and therapeutic implications. Drug Resist Updat. 2004; 7(2):97-110. DOI: 10.1016/j.drup.2004.01.004. View

18.

Ray P, Huang B, Tsuji Y . Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal. 2012; 24(5):981-90. PMC: 3454471. DOI: 10.1016/j.cellsig.2012.01.008. View

19.

Reczek C, Chandel N . ROS Promotes Cancer Cell Survival through Calcium Signaling. Cancer Cell. 2018; 33(6):949-951. DOI: 10.1016/j.ccell.2018.05.010. View

20.

Abdul-Aziz A, MacEwan D, Bowles K, Rushworth S . Oxidative stress responses and NRF2 in human leukaemia. Oxid Med Cell Longev. 2015; 2015:454659. PMC: 4396545. DOI: 10.1155/2015/454659. View