LncRNA CAI2 Contributes to Poor Prognosis of Glioma through the PI3K-Akt Signaling Pathway


Cite item

Full Text

Abstract

Aims:We aim to explore new potential therapeutic targets and markers in human glioma

Background:Gliomas are the most common malignant primary tumor in the brain.

Objective:In the present research, we evaluated the effect of CAI2, a long non-coding RNA, on the biological behaviors of glioma and explored the related molecular mechanism.

Methods:The expression of CAI2 was analyzed using qRT-PCR in 65 cases of glioma patients. The cell proliferation was determined with MTT and colony formation assays, and the PI3K-AKt signaling pathway was analyzed using western blot.

Results:CAI2 was upregulated in human glioma tissue compared with the matched, adjacent nontumor tissue and was correlated with WHO grade. Survival analyses proved that the overall survival of patients with high CAI2 expression was poor compared to that of patients with low CAI2 expression. High CAI2 expression was an independent prognostic factor in glioma. The absorbance values in the MTT assay after 96 h were .712 ± .031 for the si-control and .465 ± .018 for the si- CAI2-transfected cells, and si-CAI2 inhibited colony formation in U251 cells by approximately 80%. The levels of PI3K, p-AKt, and AKt in si-CAI2-treated cells were decreased.

Conclusion:CAI2 may promote glioma growth through the PI3K-AKt signaling pathway. This research provided a novel potential diagnostic marker for human glioma.

About the authors

Yu Jiang

Institute of Molecular Medicine, Medical College of Liaodong University

Email: info@benthamscience.net

Jinhui Zhang

Institute of Molecular Medicine, Medical College of Liaodong University

Email: info@benthamscience.net

Shengjin Yu

Institute of Molecular Medicine, Medical College of Liaodong University

Email: info@benthamscience.net

Linlin Zheng

Institute of Molecular Medicine, Medical College of Liaodong University

Email: info@benthamscience.net

Yue Shen

Institute of Molecular Medicine, Medical College of Liaodong University

Email: info@benthamscience.net

Weiwei Ju

Institute of Molecular Medicine, Medical College of Liaodong University

Email: info@benthamscience.net

Lijuan Lin

Institute of Molecular Medicine, Medical College of Liaodong University

Author for correspondence.
Email: info@benthamscience.net

References

  1. Yan, Y.; Xu, Z.; Li, Z.; Sun, L.; Gong, Z. An insight into the increasing role of LncRNAs in the pathogenesis of gliomas. Front. Mol. Neurosci., 2017, 10, 53. doi: 10.3389/fnmol.2017.00053 PMID: 28293170
  2. Dahlin, A.M.; Wibom, C.; Ghasimi, S.; Brännström, T.; Andersson, U.; Melin, B. Relation between established glioma risk variants and DNA methylation in the tumor. PLoS One, 2016, 11(10), e0163067. doi: 10.1371/journal.pone.0163067 PMID: 27780202
  3. Guo, Q.; Guan, G.F.; Cheng, W.; Zou, C.Y.; Zhu, C.; Cheng, P.; Wu, A.H. Integrated profiling identifies caveolae‐associated protein 1 as a prognostic biomarker of malignancy in glioblastoma patients. CNS Neurosci. Ther., 2019, 25(3), 343-354. doi: 10.1111/cns.13072 PMID: 30311408
  4. Liang, M.; Gao, C.; Wang, Y.; Gong, W.; Fu, S.; Cui, L.; Zhou, Z.; Chu, X.; Zhang, Y.; Liu, Q.; Zhao, X.; Zhao, B.; Yang, M.; Li, Z.; Yang, C.; Xie, X.; Yang, Y.; Gao, C. Enhanced blood–brain barrier penetration and glioma therapy mediated by T7 peptide-modified low-density lipoprotein particles. Drug Deliv., 2018, 25(1), 1652-1663. doi: 10.1080/10717544.2018.1494223 PMID: 30394123
  5. Wang, F.; Zheng, Z.; Guan, J.; Qi, D.; Zhou, S.; Shen, X.; Wang, F.; Wenkert, D.; Kirmani, B.; Solouki, T.; Fonkem, E.; Wong, E.T.; Huang, J.H.; Wu, E. Identification of a panel of genes as a prognostic biomarker for glioblastoma. E Bio. Med., 2018, 37, 68-77. doi: 10.1016/j.ebiom.2018.10.024 PMID: 30341039
  6. Dahariya, S.; Paddibhatla, I.; Kumar, S.; Raghuwanshi, S.; Pallepati, A.; Gutti, R.K. Long non-coding RNA: Classification, biogenesis and functions in blood cells. Mol. Immunol., 2019, 112, 82-92. doi: 10.1016/j.molimm.2019.04.011 PMID: 31079005
  7. Wang, L.; Yu, Z.; Sun, S.; Peng, J.; Xiao, R.; Chen, S.; Zuo, X.; Cheng, Q.; Xia, Y. Long non-coding RNAs: potential molecular biomarkers for gliomas diagnosis and prognosis. Rev. Neurosci., 2017, 28(4), 375-380. doi: 10.1515/revneuro-2016-0066 PMID: 28107175
  8. Zhang, R.; Jin, H.; Lou, F. The long non-coding RNA TP73-AS1 interacted with miR-142 to modulate brain glioma growth through HMGB1/RAGE pathway. J. Cell. Biochem., 2018, 119(4), 3007-3016. doi: 10.1002/jcb.26021 PMID: 28379612
  9. He, Z.; Wang, Y.; Huang, G.; Wang, Q.; Zhao, D.; Chen, L. The lncRNA UCA1 interacts with miR-182 to modulate glioma proliferation and migration by targeting iASPP. Arch. Biochem. Biophys., 2017, 623-624, 1-8. doi: 10.1016/j.abb.2017.01.013 PMID: 28137422
  10. Barnhill, L.M.; Williams, R.T.; Cohen, O.; Kim, Y.; Batova, A.; Mielke, J.A.; Messer, K.; Pu, M.; Bao, L.; Yu, A.L.; Diccianni, M.B. High expression of CAI2, a 9p21-embedded long noncoding RNA, contributes to advanced-stage neuroblastoma. Cancer Res., 2014, 74(14), 3753-3763. doi: 10.1158/0008-5472.CAN-13-3447 PMID: 25028366
  11. Mohamed, E.; Kumar, A.; Zhang, Y.; Wang, A.S.; Chen, K.; Lim, Y.; Shai, A.; Taylor, J.W.; Clarke, J.; Hilz, S.; Berger, M.S.; Solomon, D.A.; Costello, J.F.; Molinaro, A.M.; Phillips, J.J. PI3K/AKT/mTOR signaling pathway activity in IDH-mutant diffuse glioma and clinical implications. Neuro-oncol., 2022, 24(9), 1471-1481. doi: 10.1093/neuonc/noac064 PMID: 35287169
  12. Johnson, B.E.; Mazor, T.; Hong, C.; Barnes, M.; Aihara, K.; McLean, C.Y.; Fouse, S.D.; Yamamoto, S.; Ueda, H.; Tatsuno, K.; Asthana, S.; Jalbert, L.E.; Nelson, S.J.; Bollen, A.W.; Gustafson, W.C.; Charron, E.; Weiss, W.A.; Smirnov, I.V.; Song, J.S.; Olshen, A.B.; Cha, S.; Zhao, Y.; Moore, R.A.; Mungall, A.J.; Jones, S.J.M.; Hirst, M.; Marra, M.A.; Saito, N.; Aburatani, H.; Mukasa, A.; Berger, M.S.; Chang, S.M.; Taylor, B.S.; Costello, J.F. Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma. Science, 2014, 343(6167), 189-193. doi: 10.1126/science.1239947 PMID: 24336570
  13. Zhang, Y.; Kwok-Shing Ng, P.; Kucherlapati, M.; Chen, F.; Liu, Y.; Tsang, Y.H.; de Velasco, G.; Jeong, K.J.; Akbani, R.; Hadjipanayis, A.; Pantazi, A.; Bristow, C.A.; Lee, E.; Mahadeshwar, H.S.; Tang, J.; Zhang, J.; Yang, L.; Seth, S.; Lee, S.; Ren, X.; Song, X.; Sun, H.; Seidman, J.; Luquette, L.J.; Xi, R.; Chin, L.; Protopopov, A.; Westbrook, T.F.; Shelley, C.S.; Choueiri, T.K.; Ittmann, M.; Van Waes, C.; Weinstein, J.N.; Liang, H.; Henske, E.P.; Godwin, A.K.; Park, P.J.; Kucherlapati, R.; Scott, K.L.; Mills, G.B.; Kwiatkowski, D.J.; Creighton, C.J. A Pan-Cancer Proteogenomic Atlas of PI3K/AKT/mTOR Pathway Alterations. Cancer Cell, 2017, 31(6), 820-832.e3. doi: 10.1016/j.ccell.2017.04.013 PMID: 28528867
  14. Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature, 2008, 455(7216), 1061-1068. doi: 10.1038/nature07385 PMID: 18772890
  15. Pollack, I.F.; Hamilton, R.L.; Burger, P.C.; Brat, D.J.; Rosenblum, M.K.; Murdoch, G.H.; Nikiforova, M.N.; Holmes, E.J.; Zhou, T.; Cohen, K.J.; Jakacki, R.I. Akt activation is a common event in pediatric malignant gliomas and a potential adverse prognostic marker: A report from the Children’s Oncology Group. J. Neurooncol., 2010, 99(2), 155-163. doi: 10.1007/s11060-010-0297-3 PMID: 20607350
  16. Liu, C.; Wu, H.; Li, Y.; Shen, L.; Yu, R.; Yin, H.; Sun, T.; Sun, C.; Zhou, Y.; Du, Z. SALL4 suppresses PTEN expression to promote glioma cell proliferation viaPI3K/AKT signaling pathway. J. Neurooncol., 2017, 135(2), 263-272. doi: 10.1007/s11060-017-2589-3 PMID: 28887597
  17. Zhang, Z.Q.; Wang, X.; Xue, B.H.; Zhao, Y.; Xie, F.; Wang, S.D.; Xue, C.; Wang, Y.; Zhang, Y.S.; Qian, L.J. Chronic stress promotes glioma cell proliferation via the PI3K/Akt signaling pathway. Oncol. Rep., 2021, 46(3), 202. doi: 10.3892/or.2021.8153 PMID: 34296295
  18. Zhu, Y.; Liu, X.; Zhao, P.; Zhao, H.; Gao, W.; Wang, L. Celastrol suppresses glioma vasculogenic mimicry formation and angiogenesis by blocking the PI3K/Akt/mTOR signaling pathway. Front. Pharmacol., 2020, 11, 25. doi: 10.3389/fphar.2020.00025 PMID: 32116702
  19. Gu, Y.; Chen, T.; Li, G.; Yu, X.; Lu, Y.; Wang, H.; Teng, L. LncRNAs: emerging biomarkers in gastric cancer. Future Oncol., 2015, 11(17), 2427-2441. doi: 10.2217/fon.15.175 PMID: 26289363
  20. Mitra, S.A.; Mitra, A.P.; Triche, T.J. A central role for long non-coding RNA in cancer. Front. Genet., 2012, 3, 17. doi: 10.3389/fgene.2012.00017 PMID: 22363342
  21. Ellis, B.C.; Molloy, P.L.; Graham, L.D. CRNDE: A long non-coding RNA involved in cancer, neurobiology, and development. Front. Genet., 2012, 3, 270. doi: 10.3389/fgene.2012.00270 PMID: 23226159
  22. Diccianni, M.B.; Omura-Minamisawa, M.; Batova, A.; Le, T.; Bridgeman, L.; Yu, A.L. Frequent deregulation ofp16 and thep16/G1 cell cycle-regulatory pathway in neuroblastoma. Int. J. Cancer, 1999, 80(1), 145-154. doi: 10.1002/(SICI)1097-0215(19990105)80:13.0.CO;2-G PMID: 9935245
  23. Diccianni, M.B.; Chau, L.S.; Batova, A.; Vu, T.Q.; Yu, A.L. The p16 and p18 tumor suppressor genes in neuroblastoma: implications for drug resistance. Cancer Lett., 1996, 104(2), 183-192. doi: 10.1016/0304-3835(96)04250-4 PMID: 8665486
  24. Williams, R.T.; Barnhill, L.M.; Kuo, H.H.; Lin, W.D.; Batova, A.; Yu, A.L.; Diccianni, M.B. Chimeras of p14ARF and p16: functional hybrids with the ability to arrest growth. PLoS One, 2014, 9(2), e88219. doi: 10.1371/journal.pone.0088219 PMID: 24505435
  25. Yang, Y.; Ren, M.; Song, C.; Li, D.; Soomro, S.H.; Xiong, Y.; Zhang, H.; Fu, H. LINC00461, a long non-coding RNA, is important for the proliferation and migration of glioma cells. Oncotarget, 2017, 8(48), 84123-84139. doi: 10.18632/oncotarget.20340 PMID: 29137410
  26. Li, F.; Jin, D.; Tang, C.; Gao, D. CEP55 promotes cell proliferation and inhibits apoptosis via the PI3K/Akt/p21 signaling pathway in human glioma U251 cells. Oncol. Lett., 2018, 15(4), 4789-4796. doi: 10.3892/ol.2018.7934 PMID: 29552118
  27. Song, Y.; Zheng, S.; Wang, J.; Long, H.; Fang, L.; Wang, G.; Li, Z.; Que, T.; Liu, Y.; Li, Y.; Zhang, X.; Fang, W.; Qi, S. Hypoxia induced PLOD2 promotes proliferation, migration and in vasion via PI3K/Akt signaling in glioma. Oncotarget, 2017, 8(26), 41947-41962. doi: 10.18632/oncotarget.16710 PMID: 28410212
  28. Chen, H.; Gao, J.; Du, Z.; Zhang, X.; Yang, F.; Gao, W. Expression of factors and key components associated with the PI3K signaling pathway in colon cancer. Oncol. Lett., 2018, 15(4), 5465-5472. doi: 10.3892/ol.2018.8044 PMID: 29552187

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Bentham Science Publishers