LncRNA MIR223HG regulates ATM expression affecting proliferation, migration and apoptosis of lung adenocarcinoma cells_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

QI Kai ¹ , ZHENG Li ² , PENG Jinhua ¹ , SONG Chao ¹ , CHEN Xianglai ¹ ,  XU Jianjun ¹

1. Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330000, P. R. China;
2. Department of Gastroenterology, Nanchang First Hospital, Nanchang, Jiangxi 330000, P. R. China;

Corresponding author：

XU Jianjun, Email: xujianjun3526@163.com

Keywords：

Long non-coding RNA; MIR223HG; ataxia-telangiectasia mutated; lung adenocarcinoma

DOI：

10.7507/1671-6205.202403047

Video：

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Objective To investigate the molecular mechanisms by which the long non-coding RNA (lncRNA) MIR223HG affects the proliferation, migration and apoptosis of lung adenocarcinoma cells. Methods DNA damaging agent Zeocin was used to treat human embryo lung cell (MRC-5) and lung cancer cell (A549 and H1299), and the expression of MIR223HG was tested by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Moreover, the ataxia-telangiectasia mutated (ATM) protein and ATM pathway downstream factor Cell cycle checkpoint kinase 2 (Chk2), p53 tumor suppressor protein (p53) in the lung cancer cell (A549 and H1299) with Zeocin were also tested by qRT-PCR. Cell transfection and Transwell migration assay, colony formation assays, apoptosis assays were performed to verify the role of ATM in the expression of MIR223HG in lung adenocarcinoma. Results The expression of MIR223HG was reduced markedly in the lung cancer cells (A549 and H1299) compared with human embryo lung cell (MRC-5) after treated with Zeocin. ATM protein and its downstream factors Chk2, p53 involved in the process, and ATM regulated the expression of MIR223HG in the lung cancer cells with Zeocin. Futhermore, ATM joined in the processes that MIR223HG regulated the lung cancer cells proliferation, migration and apoptosis. Conclusions The expression of MIR223HG is related to the DNA damage response in the lung cancer, and MIR223HG regulates lung cancer cells proliferation, migration and apoptosis by ATM/Chk2/p53 pathway. MIR223HG may be a potential therapeutic target for lung adenocarcinoma treatment.

Citation： QI Kai, ZHENG Li, PENG Jinhua, SONG Chao, CHEN Xianglai, XU Jianjun. LncRNA MIR223HG regulates ATM expression affecting proliferation, migration and apoptosis of lung adenocarcinoma cells. Chinese Journal of Respiratory and Critical Care Medicine, 2025, 24(1): 42-50. doi: 10.7507/1671-6205.202403047 Copy

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18.	Wu C, Chen W, Yu F, et al. Long noncoding RNA HITTERS protects oral squamous cell carcinoma cells from endoplasmic reticulum stress-induced apoptosis via promoting MRE11-RAD50-NBS1 complex formation. Adv Sci (Weinh), 2020, 7(22): 2002747.
19.	Chaudhary R, Gryder B, Woods WS, et al. Prosurvival long noncoding RNA PINCR regulates a subset of p53 targets in human colorectal cancer cells by binding to Matrin 3. Elife, 2017, 6: e23244.
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23.	Liu J, Yao L, Zhang M, et al. Downregulation of LncRNA-XIST inhibited development of non-small cell lung cancer by activating miR-335/SOD2/ROS signal pathway mediated pyroptotic cell death. Aging (Albany NY), 2019, 11(18): 7830-7846.
24.	Geng W, Lv Z, Fan J, et al. Identification of the prognostic significance of somatic mutation-derived LncRNA signatures of genomic instability in lung adenocarcinoma. Front Cell Dev Biol, 2021, 9: 657667.
25.	Waldman T, Kinzler KW, Vogelstein B. p21 is necessary for the p53-mediated G1 arrest in human cancer cells. Cancer Res, 1995, 55(22): 5187-5190.
26.	Batista LFZ, Kaina B, Meneghini R, et al. How DNA lesions are turned into powerful killing structures: insights from UV-induced apoptosis. Mutat Res, 2009, 681(2-3): 197-208.
27.	Nogalski MT, Shenk T. HSATII RNA is induced via a noncanonical ATM-regulated DNA damage response pathway and promotes tumor cell proliferation and movement. Proc Natl Acad Sci U S A, 2020, 117(50): 31891-31901.
28.	Jiang MC, Ni JJ, Cui WY, et al. Emerging roles of lncRNA in cancer and therapeutic opportunities. Am J Cancer Res, 2019, 9(7): 1354-1366.

1. Eymery A, Horard B, El Atifi-Borel M, et al. A transcriptomic analysis of human centromeric and pericentric sequences in normal and tumor cells. Nucleic Acids Res, 2009, 37(19): 6340-6354.
2. Hall LE, Mitchell SE, O'Neill RJ. Pericentric and centromeric transcription: a perfect balance required. Chromosome Res, 2012, 20(5): 535-546.
3. Garrido-Ramos MA. Satellite DNA: An Evolving Topic. Genes (Basel), 2017, 8(9): 230.
4. Louzada S, Lopes M, Ferreira D, et al. Decoding the role of Satellite DNA in genome architecture and plasticity-an evolutionary and clinical affair. Genes (Basel), 2020, 11(1): 72.
5. Bartek J, Lukas J. DNA damage checkpoints: from initiation to recovery or adaptation. Curr Opin Cell Biol, 2007, 19(2): 238-245.
6. Ciccia A, Elledge SJ. The DNA damage response: making it safe to play with knives. Mol Cell, 2010, 40(2): 179-204.
7. Kumar R, Horikoshi N, Singh M, et al. Chromatin modifications and the DNA damage response to ionizing radiation. Front Oncol, 2013, 2: 214.
8. Lukas J, Lukas C, Bartek J. More than just a focus: the chromatin response to DNA damage and its role in genome integrity maintenance. Nat Cell Biol, 2011, 13(10): 1161-1169.
9. Chen R, Wold MS. Replication protein A: single-stranded DNA’s first responder: dynamic DNA-interactions allow replication protein A to direct single-strand DNA intermediates into different pathways for synthesis or repair. Bioessays, 2014, 36(12): 1156-1161.
10. Sugrue T, Brown JA, Lowndes NF, et al. Multiple facets of the DNA damage response contribute to the radioresistance of mouse mesenchymal stromal cell lines. Stem Cells, 2013, 31(1): 137-145.
11. Foltánková V, Legartová S, Kozubek S, et al. DNA-damage response in chromatin of ribosomal genes and the surrounding genome. Gene, 2013, 522(2): 156-167.
12. Patil M, Pabla N, Dong Z. Checkpoint kinase 1 in DNA damage response and cell cycle regulation. Cell Mol Life Sci, 2013, 70(21): 4009-4021.
13. Barba M, Vici P, Pizzuti L, et al. Body mass index modifies the relationship between γ-H2AX, a DNA damage biomarker, and pathological complete response in triple-negative breast cancer. BMC Cancer, 2017, 17(1): 101.
14. Thomasova D, Anders HJ. Cell cycle control in the kidney. Nephrol Dial Transplant, 2015, 30(10): 1622-1630.
15. Zhu S, Pabla N, Tang C, et al. DNA damage response in cisplatin-induced nephrotoxicity. Arch Toxicol, 2015, 89(12): 2197-2205.
16. Su M, Wang H, Wang W, et al. LncRNAs in DNA damage response and repair in cancer cells. Acta Biochim Biophys Sin (Shanghai), 2018, 50(5): 433-439.
17. Lou MM, Tang XQ, Wang GM, et al. Long noncoding RNA BS-DRL1 modulates the DNA damage response and genome stability by interacting with HMGB1 in neurons. Nat Commun, 2021, 12(1): 4075.
18. Wu C, Chen W, Yu F, et al. Long noncoding RNA HITTERS protects oral squamous cell carcinoma cells from endoplasmic reticulum stress-induced apoptosis via promoting MRE11-RAD50-NBS1 complex formation. Adv Sci (Weinh), 2020, 7(22): 2002747.
19. Chaudhary R, Gryder B, Woods WS, et al. Prosurvival long noncoding RNA PINCR regulates a subset of p53 targets in human colorectal cancer cells by binding to Matrin 3. Elife, 2017, 6: e23244.
20. Wang M, Mao C, Ouyang L, et al. Long noncoding RNA LINC00336 inhibits ferroptosis in lung cancer by functioning as a competing endogenous RNA. Cell Death Differ, 2019, 26(11): 2329-2343.
21. Zappa C, Mousa SA. Non-small cell lung cancer: current treatment and future advances. Transl Lung Cancer Res, 2016, 5(3): 288-300.
22. Yu F, Liang M, Wu W, et al. Upregulation of long non-coding RNA GCC2-AS1 facilitates malignant phenotypes and correlated with unfavorable prognosis for lung adenocarcinoma. Front Oncol, 2021, 10: 628608.
23. Liu J, Yao L, Zhang M, et al. Downregulation of LncRNA-XIST inhibited development of non-small cell lung cancer by activating miR-335/SOD2/ROS signal pathway mediated pyroptotic cell death. Aging (Albany NY), 2019, 11(18): 7830-7846.
24. Geng W, Lv Z, Fan J, et al. Identification of the prognostic significance of somatic mutation-derived LncRNA signatures of genomic instability in lung adenocarcinoma. Front Cell Dev Biol, 2021, 9: 657667.
25. Waldman T, Kinzler KW, Vogelstein B. p21 is necessary for the p53-mediated G1 arrest in human cancer cells. Cancer Res, 1995, 55(22): 5187-5190.
26. Batista LFZ, Kaina B, Meneghini R, et al. How DNA lesions are turned into powerful killing structures: insights from UV-induced apoptosis. Mutat Res, 2009, 681(2-3): 197-208.
27. Nogalski MT, Shenk T. HSATII RNA is induced via a noncanonical ATM-regulated DNA damage response pathway and promotes tumor cell proliferation and movement. Proc Natl Acad Sci U S A, 2020, 117(50): 31891-31901.
28. Jiang MC, Ni JJ, Cui WY, et al. Emerging roles of lncRNA in cancer and therapeutic opportunities. Am J Cancer Res, 2019, 9(7): 1354-1366.

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LncRNA MIR223HG regulates ATM expression affecting proliferation, migration and apoptosis of lung adenocarcinoma cells

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