Skip to main content
Top
Published in: Diagnostic Pathology 1/2021

Open Access 01-12-2021 | NSCLC | Research

LncRNA GAS5 modulates the progression of non-small cell lung cancer through repressing miR-221-3p and up-regulating IRF2

Authors: Juan Ma, Haiyan Miao, Haiyun Zhang, Jingjing Ren, Shengyan Qu, Jing Da, Feifan Xu, Huan Zhao

Published in: Diagnostic Pathology | Issue 1/2021

Login to get access

Abstract

Background

Long non-coding RNA growth arrest specific 5 (GAS5) is a regulator in non-small cell lung cancer (NSCLC) progression. Nonetheless, the mechanism by which GAS5 exerts its biological function in NSCLC cells remains unclear.

Methods

GAS5, miR-221-3p relative expression levels in NSCLC tissues and cells were examined by qPCR. After gain-of-function and loss-of-function models were established, the viability of H1299 and A549 cells were examined by CCK-8 and EdU assays. Cell migration and invasion were examined by the Transwell experiment. The binding sequence of GAS5 for miR-221-3p was confirmed by the dual-luciferase reporter gene experiment. The regulatory function of GAS5 and miR-221-3p on IRF2 was investigated by Western blot.

Results

GAS5 expression was down-modulated in NSCLC tissues and cell lines. GAS5 overexpression restrained the proliferation, migration and invasion of NSCLC cells, while miR-221-3p, which was targeted and negatively modulated by GAS5, worked oppositely. Restoration of miR-221-3p markedly reversed the effects of GAS5 on NSCLC cells. Additionally, GAS5 increased IRF2 expression in NSCLC cells by repressing miR-221-3p.

Conclusions

GAS5 blocks the progression of NSCLC partly via increasing IRF2 expression level via repressing miR-221-3p.
Literature
1.
go back to reference Rotow J, Bivona TG. Understanding and targeting resistance mechanisms in NSCLC. Nat Rev Cancer. 2017;17(11):637–58.CrossRef Rotow J, Bivona TG. Understanding and targeting resistance mechanisms in NSCLC. Nat Rev Cancer. 2017;17(11):637–58.CrossRef
2.
go back to reference Goldstraw P, Ball D, Jett JR, Le CT, Lim E, Nicholson AG, et al. Non- small-cell lung cancer. Lancet. 2011;378:1727–40.CrossRef Goldstraw P, Ball D, Jett JR, Le CT, Lim E, Nicholson AG, et al. Non- small-cell lung cancer. Lancet. 2011;378:1727–40.CrossRef
3.
go back to reference Zhang YL, Li XB, Hou YX, Fang NZ, You JC, Zhou QH. The lncRNA XIST exhibits oncogenic properties via regulation of miR-449a and Bcl-2 in human non-small cell lung cancer. Acta Pharmacol Sin. 2017;38(3):371–81.CrossRef Zhang YL, Li XB, Hou YX, Fang NZ, You JC, Zhou QH. The lncRNA XIST exhibits oncogenic properties via regulation of miR-449a and Bcl-2 in human non-small cell lung cancer. Acta Pharmacol Sin. 2017;38(3):371–81.CrossRef
4.
go back to reference Li J, Yang C, Li Y, Chen A, Li L, You Z. LncRNA GAS5 suppresses ovarian cancer by inducing inflammasome formation. Biosci Rep. 2018;38(2):BSR20171150.CrossRef Li J, Yang C, Li Y, Chen A, Li L, You Z. LncRNA GAS5 suppresses ovarian cancer by inducing inflammasome formation. Biosci Rep. 2018;38(2):BSR20171150.CrossRef
5.
go back to reference Dong L, Li G, Li Y, Zhu Z. Upregulation of Long Noncoding RNA GAS5 Inhibits Lung Cancer Cell Proliferation and Metastasis via miR-205/PTEN Axis. Med Sci Monit. 2019;25:2311–9.CrossRef Dong L, Li G, Li Y, Zhu Z. Upregulation of Long Noncoding RNA GAS5 Inhibits Lung Cancer Cell Proliferation and Metastasis via miR-205/PTEN Axis. Med Sci Monit. 2019;25:2311–9.CrossRef
6.
go back to reference Wu XG, Zhou CF, Zhang YM, Yan RM, Wei WF, Chen XJ, Yi HY, Liang LJ, Fan LS, Liang L, Wu S, Wang W. Cancer-derived exosomal miR-221-3p promotes angiogenesis by targeting THBS2 in cervical squamous cell carcinoma. Angiogenesis. 2019;22(3):397–410.CrossRef Wu XG, Zhou CF, Zhang YM, Yan RM, Wei WF, Chen XJ, Yi HY, Liang LJ, Fan LS, Liang L, Wu S, Wang W. Cancer-derived exosomal miR-221-3p promotes angiogenesis by targeting THBS2 in cervical squamous cell carcinoma. Angiogenesis. 2019;22(3):397–410.CrossRef
7.
go back to reference Wu Q, Ren X, Zhang Y, Fu X, Li Y, Peng Y, Xiao Q, Li T, Ouyang C, Hu Y, Zhang Y, Zhou W, Yan W, Guo K, Li W, Hu Y, Yang X, Shu G, Xue H, Wei Z, Luo Y, Yin G. miR-221-3p targets ARF4 and inhibits the proliferation and migration of epithelial ovarian cancer cells. Biochem Biophys Res Commun. 2018;497(4):1162–70.CrossRef Wu Q, Ren X, Zhang Y, Fu X, Li Y, Peng Y, Xiao Q, Li T, Ouyang C, Hu Y, Zhang Y, Zhou W, Yan W, Guo K, Li W, Hu Y, Yang X, Shu G, Xue H, Wei Z, Luo Y, Yin G. miR-221-3p targets ARF4 and inhibits the proliferation and migration of epithelial ovarian cancer cells. Biochem Biophys Res Commun. 2018;497(4):1162–70.CrossRef
8.
go back to reference Jin JJ, Liu YH, Si JM, Ni R, Wang J. Overexpression of miR-1290 contributes to cell proliferation and invasion of non small cell lung cancer by targeting interferon regulatory factor 2. Int J Biochem Cell Biol. 2018;95:113–20.CrossRef Jin JJ, Liu YH, Si JM, Ni R, Wang J. Overexpression of miR-1290 contributes to cell proliferation and invasion of non small cell lung cancer by targeting interferon regulatory factor 2. Int J Biochem Cell Biol. 2018;95:113–20.CrossRef
9.
go back to reference Feng J, Wang M, Li M, Yang J, Jia J, Liu L, Zhou J, Zhang C, Wang X. Serum miR-221-3p as a new potential biomarker for depressed mood in perioperative patients. Brain Res. 2019;1720:146296.CrossRef Feng J, Wang M, Li M, Yang J, Jia J, Liu L, Zhou J, Zhang C, Wang X. Serum miR-221-3p as a new potential biomarker for depressed mood in perioperative patients. Brain Res. 2019;1720:146296.CrossRef
10.
go back to reference Santos RM, Moreno C, Zhang WC. Non-Coding RNAs in Lung Tumor Initiation and Progression. Int J Mol Sci. 2020;21(8):2774.CrossRef Santos RM, Moreno C, Zhang WC. Non-Coding RNAs in Lung Tumor Initiation and Progression. Int J Mol Sci. 2020;21(8):2774.CrossRef
11.
go back to reference Lambrou GI, Hatziagapiou K, Zaravinos A. The Non-Coding RNA GAS5 and Its Role in Tumor Therapy-Induced Resistance. Int J Mol Sci. 2020;21(20):7633.CrossRef Lambrou GI, Hatziagapiou K, Zaravinos A. The Non-Coding RNA GAS5 and Its Role in Tumor Therapy-Induced Resistance. Int J Mol Sci. 2020;21(20):7633.CrossRef
12.
go back to reference Yang X, Xie Z, Lei X, Gan R. Long non-coding RNA GAS5 in human cancer. Oncol Lett. 2020;20(3):2587–94.CrossRef Yang X, Xie Z, Lei X, Gan R. Long non-coding RNA GAS5 in human cancer. Oncol Lett. 2020;20(3):2587–94.CrossRef
13.
go back to reference Ni W, Yao S, Zhou Y, Liu Y, Huang P, Zhou A, Liu J, Che L, Li J. Long noncoding RNA GAS5 inhibits progression of colorectal cancer by interacting with and triggering YAP phosphorylation and degradation and is negatively regulated by the m6A reader YTHDF3. Mol Cancer. 2019;18(1):143.CrossRef Ni W, Yao S, Zhou Y, Liu Y, Huang P, Zhou A, Liu J, Che L, Li J. Long noncoding RNA GAS5 inhibits progression of colorectal cancer by interacting with and triggering YAP phosphorylation and degradation and is negatively regulated by the m6A reader YTHDF3. Mol Cancer. 2019;18(1):143.CrossRef
14.
go back to reference Li C, Lv Y, Shao C, Chen C, Zhang T, Wei Y, Fan H, Lv T, Liu H, Song Y. Tumor-derived exosomal lncRNA GAS5 as a biomarker for early-stage non-small-cell lung cancer diagnosis. J Cell Physiol. 2019;234(11):20721–7.CrossRef Li C, Lv Y, Shao C, Chen C, Zhang T, Wei Y, Fan H, Lv T, Liu H, Song Y. Tumor-derived exosomal lncRNA GAS5 as a biomarker for early-stage non-small-cell lung cancer diagnosis. J Cell Physiol. 2019;234(11):20721–7.CrossRef
15.
go back to reference Cao L, Chen J, Ou B, Liu C, Zou Y, Chen Q. GAS5 knockdown reduces the chemo-sensitivity of non-small cell lung cancer (NSCLC) cell to cisplatin (DDP) through regulating miR-21/PTEN axis. Biomed Pharmacother. 2017;93:570–9.CrossRef Cao L, Chen J, Ou B, Liu C, Zou Y, Chen Q. GAS5 knockdown reduces the chemo-sensitivity of non-small cell lung cancer (NSCLC) cell to cisplatin (DDP) through regulating miR-21/PTEN axis. Biomed Pharmacother. 2017;93:570–9.CrossRef
16.
go back to reference Chen L, Ren P, Zhang Y, Gong B, Yu D, Sun X. Long non-coding RNA GAS5 increases the radiosensitivity of A549 cells through interaction with the miR-21/PTEN/Akt axis. Oncol Rep. 2020;43(3):897–907.PubMedPubMedCentral Chen L, Ren P, Zhang Y, Gong B, Yu D, Sun X. Long non-coding RNA GAS5 increases the radiosensitivity of A549 cells through interaction with the miR-21/PTEN/Akt axis. Oncol Rep. 2020;43(3):897–907.PubMedPubMedCentral
17.
go back to reference Song Q, An Q, Niu B, Lu X, Zhang N, Cao X. Role of miR-221/222 in Tumor Development and the Underlying Mechanism. J Oncol. 2019;2019:7252013.PubMedPubMedCentral Song Q, An Q, Niu B, Lu X, Zhang N, Cao X. Role of miR-221/222 in Tumor Development and the Underlying Mechanism. J Oncol. 2019;2019:7252013.PubMedPubMedCentral
18.
go back to reference Dong Y, Zhang N, Zhao S, Chen X, Li F, Tao X. miR-221-3p and miR-15b-5p promote cell proliferation and invasion by targeting Axin2 in liver cancer. Oncol Lett. 2019;18(6):6491–500.PubMedPubMedCentral Dong Y, Zhang N, Zhao S, Chen X, Li F, Tao X. miR-221-3p and miR-15b-5p promote cell proliferation and invasion by targeting Axin2 in liver cancer. Oncol Lett. 2019;18(6):6491–500.PubMedPubMedCentral
19.
go back to reference Li F, Xu JW, Wang L, Liu H, Yan Y, Hu SY. MicroRNA-221-3p is up-regulated and serves as a potential biomarker in pancreatic cancer. Artif Cells Nanomed Biotechnol. 2018;46(3):482–7.CrossRef Li F, Xu JW, Wang L, Liu H, Yan Y, Hu SY. MicroRNA-221-3p is up-regulated and serves as a potential biomarker in pancreatic cancer. Artif Cells Nanomed Biotechnol. 2018;46(3):482–7.CrossRef
20.
go back to reference Yin G, Zhang B, Li J. miR-221-3p promotes the cell growth of nonsmall cell lung cancer by targeting p27. Mol Med Rep. 2019;20(1):604–12.PubMedPubMedCentral Yin G, Zhang B, Li J. miR-221-3p promotes the cell growth of nonsmall cell lung cancer by targeting p27. Mol Med Rep. 2019;20(1):604–12.PubMedPubMedCentral
21.
go back to reference Zong Y, Zhang Y, Sun X, Xu T, Cheng X, Qin Y. miR-221/222 promote tumor growth and suppress apoptosis by targeting lncRNA GAS5 in breast cancer. Biosci Rep. 2019;39(1):BSR20181859.CrossRef Zong Y, Zhang Y, Sun X, Xu T, Cheng X, Qin Y. miR-221/222 promote tumor growth and suppress apoptosis by targeting lncRNA GAS5 in breast cancer. Biosci Rep. 2019;39(1):BSR20181859.CrossRef
22.
go back to reference Chen Z, Pan T, Jiang D, Jin L, Geng Y, Feng X, Shen A, Zhang L. The lncRNA-GAS5/miR-221-3p/DKK2 Axis Modulates ABCB1-Mediated Adriamycin Resistance of Breast Cancer via the Wnt/β-Catenin Signaling Pathway. Mol Ther Nucleic Acids. 2020;19:1434–48.CrossRef Chen Z, Pan T, Jiang D, Jin L, Geng Y, Feng X, Shen A, Zhang L. The lncRNA-GAS5/miR-221-3p/DKK2 Axis Modulates ABCB1-Mediated Adriamycin Resistance of Breast Cancer via the Wnt/β-Catenin Signaling Pathway. Mol Ther Nucleic Acids. 2020;19:1434–48.CrossRef
23.
go back to reference Yi Y, Wu H, Gao Q, He HW, Li YW, Cai XY, Wang JX, Zhou J, Cheng YF, Jin JJ, Fan J, Qiu SJ. Interferon regulatory factor (IRF)-1 and IRF-2 are associated with prognosis and tumor invasion in HCC. Ann Surg Oncol. 2013;20(1):267–76.CrossRef Yi Y, Wu H, Gao Q, He HW, Li YW, Cai XY, Wang JX, Zhou J, Cheng YF, Jin JJ, Fan J, Qiu SJ. Interferon regulatory factor (IRF)-1 and IRF-2 are associated with prognosis and tumor invasion in HCC. Ann Surg Oncol. 2013;20(1):267–76.CrossRef
24.
go back to reference Chen YJ, Wu H, Zhu JM, Li XD, Luo SW, Dong L, Liu TT, Shen XZ. MicroRNA-18a modulates P53 expression by targeting IRF2 in gastric cancer patients. J Gastroenterol Hepatol. 2016;31(1):155–63.CrossRef Chen YJ, Wu H, Zhu JM, Li XD, Luo SW, Dong L, Liu TT, Shen XZ. MicroRNA-18a modulates P53 expression by targeting IRF2 in gastric cancer patients. J Gastroenterol Hepatol. 2016;31(1):155–63.CrossRef
25.
go back to reference Kriegsman BA, Vangala P, Chen BJ, Meraner P, Brass AL, Garber M, Rock KL. Frequent Loss of IRF2 in Cancers Leads to Immune Evasion through Decreased MHC Class I Antigen Presentation and Increased PD-L1 Expression. J Immunol. 2019;203(7):1999–2010.CrossRef Kriegsman BA, Vangala P, Chen BJ, Meraner P, Brass AL, Garber M, Rock KL. Frequent Loss of IRF2 in Cancers Leads to Immune Evasion through Decreased MHC Class I Antigen Presentation and Increased PD-L1 Expression. J Immunol. 2019;203(7):1999–2010.CrossRef
26.
go back to reference Liang C, Zhang X, Wang HM, Liu XM, Zhang XJ, Zheng B, Qian GR, Ma ZL. MicroRNA-18a-5p functions as an oncogene by directly targeting IRF2 in lung cancer. Cell Death Dis. 2017;8(5):e2764.CrossRef Liang C, Zhang X, Wang HM, Liu XM, Zhang XJ, Zheng B, Qian GR, Ma ZL. MicroRNA-18a-5p functions as an oncogene by directly targeting IRF2 in lung cancer. Cell Death Dis. 2017;8(5):e2764.CrossRef
Metadata
Title
LncRNA GAS5 modulates the progression of non-small cell lung cancer through repressing miR-221-3p and up-regulating IRF2
Authors
Juan Ma
Haiyan Miao
Haiyun Zhang
Jingjing Ren
Shengyan Qu
Jing Da
Feifan Xu
Huan Zhao
Publication date
01-12-2021
Publisher
BioMed Central
Keywords
NSCLC
NSCLC
Published in
Diagnostic Pathology / Issue 1/2021
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/s13000-021-01108-0

Other articles of this Issue 1/2021

Diagnostic Pathology 1/2021 Go to the issue