Inhibition of LncRNA LINC00461/miR-216a/aquaporin 4 Pathway Suppresses Cell Proliferation, Migration, Invasion, and Chemoresistance in Glioma

Overview

Journal Open Life Sci

Specialty Biology

Date 2021 Apr 5

PMID 33817241

Citations 10

Authors

Yanguo Peng

Wangchun Wu

Zhanfang Shang

Wei Li

Shuiyu Chen

Affiliations

Soon will be listed here.

Abstract

Long noncoding RNA (lncRNA) LINC00461 (LINC00461) is reported to be related to glioma progression. However, the mechanism of LINC00461 in glioma remains unclear. Expression of LINC00461, miRNA (miR)-216a, and aquaporin 4 (AQP4) was detected using real-time quantitative PCR (RT-qPCR) and western blotting. Proliferation, temozolomide (TMZ) resistance, migration, and invasion were assessed by MTT, colony formation, and transwell assays, respectively. The target binding among miR-216a, LINC00461, and AQP4 was confirmed by the luciferase reporter assay. The tumor growth was monitored in the xenograft experiment. LINC00461 was upregulated, and miR-216a was downregulated in glioma tissues and cells, and LINC00461 upregulation was correlated with large tumor size, higher WHO grade and recurrence, and poor overall survival. LINC00461 knockdown suppressed cell viability, abilities of cell cloning and migration and invasion, and TMZ resistance in glioma. Mechanically, LINC00461 was confirmed to sponge miR-216a to affect AQP4 expression. Rescue assays verified that miR-216a downregulation or AQP4 upregulation abrogated the inhibitory effect of LINC00461 knockdown on cell proliferation, migration, invasion, and TMZ resistance . Moreover, LINC00461 downregulation blocked the glioma tumor growth In conclusion, LINC00461 knockdown inhibits glioma cell proliferation, migration, invasion, and TMZ resistance through miR-216a/AQP4 axis, suggesting LINC00461 as an oncogene in glioma progression.

Citing Articles

Update on the intriguing roles of AQP4 expression and redistribution in the progression and treatment of glioma.

Lan Y, Zou S, Chen R Ann Med. 2024; 56(1):2401111.

PMID: 39247976 PMC: 11385637. DOI: 10.1080/07853890.2024.2401111.

Non-coding RNAs and Aquaporin 4: Their Role in the Pathogenesis of Neurological Disorders.

Yaghoobi Z, Seyed Bagher Nazeri S, Asadi A, Derafsh E, Taheri A, Tamtaji Z Neurochem Res. 2023; 49(3):583-596.

PMID: 38114727 DOI: 10.1007/s11064-023-04067-8.

Molecular mechanisms of microRNA-216a during tumor progression.

Hamidi A, Taghehchian N, Zangouei A, Akhlaghipour I, Maharati A, Basirat Z Cancer Cell Int. 2023; 23(1):19.

PMID: 36740668 PMC: 9899407. DOI: 10.1186/s12935-023-02865-2.

Aquaporin-mediated dysregulation of cell migration in disease states.

Smith I, Banerjee S, Moses A, Stroka K Cell Mol Life Sci. 2023; 80(2):48.

PMID: 36682037 PMC: 10280779. DOI: 10.1007/s00018-022-04665-9.

Identification of the prognostic and immunological roles of aquaporin 4: A potential target for survival and immunotherapy in glioma patients.

Lan Y, Nie T, Zou S Front Cell Neurosci. 2022; 16:1061428.

PMID: 36523816 PMC: 9744806. DOI: 10.3389/fncel.2022.1061428.

References

Deguchi S, Katsushima K, Hatanaka A, Shinjo K, Ohka F, Wakabayashi T . Oncogenic effects of evolutionarily conserved noncoding RNA ECONEXIN on gliomagenesis. Oncogene. 2017; 36(32):4629-4640. DOI: 10.1038/onc.2017.88. View

Jansen M, Yip S, Louis D . Molecular pathology in adult gliomas: diagnostic, prognostic, and predictive markers. Lancet Neurol. 2010; 9(7):717-26. PMC: 3079431. DOI: 10.1016/S1474-4422(10)70105-8. View

Ke J, Yao Y, Zheng J, Wang P, Liu Y, Ma J . Knockdown of long non-coding RNA HOTAIR inhibits malignant biological behaviors of human glioma cells via modulation of miR-326. Oncotarget. 2015; 6(26):21934-49. PMC: 4673137. DOI: 10.18632/oncotarget.4290. View

Zhang J, Xu K, Shi L, Zhang L, Zhao Z, Xu H . Overexpression of MicroRNA-216a Suppresses Proliferation, Migration, and Invasion of Glioma Cells by Targeting Leucine-Rich Repeat-Containing G Protein-Coupled Receptor 5. Oncol Res. 2017; 25(8):1317-1327. PMC: 7840945. DOI: 10.3727/096504017X14874323871217. View

Wang R, Li Y, Zhu G, Tian B, Zeng W, Yang Y . Long noncoding RNA CASC2 predicts the prognosis of glioma patients and functions as a suppressor for gliomas by suppressing Wnt/β-catenin signaling pathway. Neuropsychiatr Dis Treat. 2017; 13:1805-1813. PMC: 5513825. DOI: 10.2147/NDT.S137171. View

Veliz I, Loo Y, Castillo O, Karachaliou N, Nigro O, Rosell R . Advances and challenges in the molecular biology and treatment of glioblastoma-is there any hope for the future?. Ann Transl Med. 2015; 3(1):7. PMC: 4293478. DOI: 10.3978/j.issn.2305-5839.2014.10.06. View

Wang W, Li Y, Ma Q, Yan H, Su W . Differentiation antagonizing non-protein coding RNA modulates the proliferation, migration, and angiogenesis of glioma cells by targeting the miR-216a/LGR5 axis and the PI3K/AKT signaling pathway. Onco Targets Ther. 2019; 12:2439-2449. PMC: 6497507. DOI: 10.2147/OTT.S196851. View

Yang L, Wang X, Zhen S, Zhang S, Kang D, Lin Z . Aquaporin-4 upregulated expression in glioma tissue is a reaction to glioma-associated edema induced by vascular endothelial growth factor. Oncol Rep. 2012; 28(5):1633-8. DOI: 10.3892/or.2012.1973. View

Cai H, Xue Y, Wang P, Wang Z, Li Z, Hu Y . The long noncoding RNA TUG1 regulates blood-tumor barrier permeability by targeting miR-144. Oncotarget. 2015; 6(23):19759-79. PMC: 4637319. DOI: 10.18632/oncotarget.4331. View

10.

Katsushima K, Natsume A, Ohka F, Shinjo K, Hatanaka A, Ichimura N . Targeting the Notch-regulated non-coding RNA TUG1 for glioma treatment. Nat Commun. 2016; 7:13616. PMC: 5150648. DOI: 10.1038/ncomms13616. View

11.

Zheng Y, Pan C, Chen M, Pei A, Xie L, Zhu S . miR‑29a ameliorates ischemic injury of astrocytes in vitro by targeting the water channel protein aquaporin 4. Oncol Rep. 2019; 41(3):1707-1717. PMC: 6365700. DOI: 10.3892/or.2019.6961. View

12.

Cai H, Liu X, Zheng J, Xue Y, Ma J, Xi Z . Long non-coding RNA taurine upregulated 1 enhances tumor-induced angiogenesis through inhibiting microRNA-299 in human glioblastoma. Oncogene. 2016; 36(3):318-331. DOI: 10.1038/onc.2016.212. View

13.

Papadopoulos M, Saadoun S . Key roles of aquaporins in tumor biology. Biochim Biophys Acta. 2014; 1848(10 Pt B):2576-83. DOI: 10.1016/j.bbamem.2014.09.001. View

14.

Sepramaniam S, Armugam A, Lim K, Karolina D, Swaminathan P, Tan J . MicroRNA 320a functions as a novel endogenous modulator of aquaporins 1 and 4 as well as a potential therapeutic target in cerebral ischemia. J Biol Chem. 2010; 285(38):29223-30. PMC: 2937953. DOI: 10.1074/jbc.M110.144576. View

15.

Liu L, Cui S, Wan T, Li X, Tian W, Zhang R . Long non-coding RNA HOTAIR acts as a competing endogenous RNA to promote glioma progression by sponging miR-126-5p. J Cell Physiol. 2018; 233(9):6822-6831. DOI: 10.1002/jcp.26432. View

16.

Zheng L, Cheng W, Wang X, Yang Z, Zhou X, Pan C . Overexpression of MicroRNA-145 Ameliorates Astrocyte Injury by Targeting Aquaporin 4 in Cerebral Ischemic Stroke. Biomed Res Int. 2017; 2017:9530951. PMC: 5615955. DOI: 10.1155/2017/9530951. View

17.

Ding T, Gu F, Fu L, Ma Y . Aquaporin-4 in glioma invasion and an analysis of molecular mechanisms. J Clin Neurosci. 2010; 17(11):1359-61. DOI: 10.1016/j.jocn.2010.02.014. View

18.

Yu X, Li Z . Serum microRNAs as potential noninvasive biomarkers for glioma. Tumour Biol. 2015; 37(2):1407-10. DOI: 10.1007/s13277-015-4515-7. View

19.

Rynkeviciene R, Simiene J, Strainiene E, Stankevicius V, Usinskiene J, Kaubriene E . Non-Coding RNAs in Glioma. Cancers (Basel). 2018; 11(1). PMC: 6356972. DOI: 10.3390/cancers11010017. View

20.

Louis D, Ohgaki H, Wiestler O, Cavenee W, Burger P, Jouvet A . The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007; 114(2):97-109. PMC: 1929165. DOI: 10.1007/s00401-007-0243-4. View