NEAT1調控miRNA在肺癌中作用機制研究進展_Chinese Journal of Respiratory and Critical Care Medicine

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宋承鑫 ^1,2 , 康麗 ¹ , 鄭丹丹 ¹ , 馬起虹 ¹ , 馬新月 ¹ ,  張甲翠 ²

1. ;
2. ;

Corresponding?author：

張甲翠, Email: zjc1504059310@163.com

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DOI：

10.7507/1671-6205.202506019

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Citation： 宋承鑫, 康麗, 鄭丹丹, 馬起虹, 馬新月, 張甲翠. NEAT1調控miRNA在肺癌中作用機制研究進展. Chinese Journal of Respiratory and Critical Care Medicine, 2026, 25(3): 223-228. doi: 10.7507/1671-6205.202506019 Copy

1.	Smolarz B, ?ukasiewicz H, Samulak D, et al. Lung cancer-epidemiology, pathogenesis, treatment and molecular aspect (review of literature). Int J Mol Sci, 2025, 26(5): 2049.
2.	Bouchard N, Daaboul N. Lung cancer: targeted therapy in 2025. Curr Oncol, 2025, 32(3): 146.
3.	Jeon H, Wang S, Song J, et al. Update 2025: Management of non-small-cell lung cancer. Lung, 2025, 203(1): 53.
4.	Zhang S, Guo J, He Y, et al. Roles of lncRNA in the crosstalk between osteogenesis and angiogenesis in the bone microenvironment. J Zhejiang Univ Sci B, 2025, 26(2): 107-123.
5.	Suliman M, Saleh RO, Chandra M, et al. Macrophage-derived lncRNAs in cancer: regulators of tumor progression and therapeutic targets. Med Oncol, 2025, 42(4): 91.
6.	Shi L, Li B, Tan J, et al. Exosomal lncRNA Mir100hg from lung cancer stem cells activates H3K14 lactylation to enhance metastatic activity in non-stem lung cancer cells. J Nanobiotechnology, 2025, 23(1): 156.
7.	De Domenico S, La Banca V, D'Amico S, et al. Defining the transcriptional routes controlling lncRNA NEAT1 expression: implications in cellular stress response, inflammation, and differentiation. Discov Oncol, 2025, 16(1): 768.
8.	Gu J, Wang Q, Mo J, et al. NEAT1 promotes the perineural invasion of pancreatic cancer via the E2F1/GDNF axis. Cancer Lett, 2025, 613: 217497.
9.	Cheng N, Guo Y. Long Noncoding RNA NEAT1 Promotes Nasopharyngeal carcinoma progression through regulation of miR-124/NF-κB Pathway. Onco Targets Ther, 2023, 16: 639-640.
10.	Chen D, Wang J, Li Y, et al. LncRNA NEAT1 suppresses cellular senescence in hepatocellular carcinoma via KIF11-dependent repression of CDKN2A. Clin Transl Med, 2023, 13(9): e1418.
11.	Hu Z, Chen J, Meng P, et al. Association between NEAT1 polymorphism and the risk of lung cancer: A protocol for systematic review and meta-analysis. Medicine (Baltimore), 2021, 100(16): e25478.
12.	Wang S, Cui Z, Li H, et al. LncRNA NEAT1 polymorphisms and lung cancer susceptibility in a Chinese Northeast Han Population: a case-control study. Pathol Res Pract, 2019, 215(12): 152723.
13.	Wu YC, Ku MH, Huang WL, et al. NEAT1 in ovarian cancer: a key regulator of tumor progression, follicular fluid dynamics, and therapeutic resistance. Anticancer Res, 2025, 45(3): 825-842.
14.	Zhang M, Weng W, Zhang Q, et al. The lncRNA NEAT1 activates Wnt/β-catenin signaling and promotes colorectal cancer progression via interacting with DDX5. J Hematol Oncol, 2018, 11(1): 113.
15.	Skeparnias I, Zhang J. Structural basis of NEAT1 lncRNA maturation and menRNA instability. Nat Struct Mol Biol, 2024, 31(11): 1650-1654.
16.	Hirose T, Yamazaki T, Nakagawa S. Molecular anatomy of the architectural NEAT1 noncoding RNA: The domains, interactors, and biogenesis pathway required to build phase-separated nuclear paraspeckles. Wiley Interdiscip Rev RNA, 2019, 10(6): e1545.
17.	Weghorst F, Torres Marcén M, Faridi G, et al. Deep conservation and unexpected evolutionary history of neighboring lncRNAs MALAT1 and NEAT1. J Mol Evol, 2024, 92(1): 30-41.
18.	Wu D, Li H, Wang J, et al. LncRNA NEAT1 promotes gastric cancer progression via miR-1294/AKT1 axis. Open Med (Wars), 2020 Oct 9;15(1): 1028-1038.
19.	Zhang M, Guo J, Liu L, et al. The role of long non-coding RNA, nuclear enriched abundant transcript 1 (NEAT1) in cancer and other pathologies. Biochem Genet, 2022, 60(3): 843-867.
20.	Fu X, Deng X, Xiao W, et al. Downregulation of NEAT1 sensitizes gemcitabine-resistant pancreatic cancer cells to gemcitabine through modulation of the miR-506-3p/ZEB2/EMT axis. Am J Cancer Res, 2021, 11(8): 3841-3856.
21.	An Y, Huang F, Tan X, et al. Exosomes of adipose tissue-derived stem cells promote wound healing by sponging miR-17-5p and inducing autophagy protein Ulk1. Plast Reconstr Surg, 2023, 151(5): 1016-1028.
22.	Sweef O, Mahfouz R, Ta?c?o?lu T, et al. Decoding lncRNA in COPD: unveiling prognostic and diagnostic power and their driving role in lung cancer progression. Int J Mol Sci, 2024, 25(16): 9001.
23.	Kahraman DT, Bozgeyik E, Guven H, et al. Long non-coding RNA signatures in non-small cell lung cancer and their clinicopathological significance. Pathol Res Pract, 2024, 253: 154946.
24.	Li Y, Zhou B, Yang Y, et al. Expression and clinical relevance of serum lncRNA NEAT1 and microRNA-31 in patients with advanced lung cancer and pulmonary infection. Altern Ther Health Med, 2024, 19: AT9614.
25.	Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell, 1993, 75(5): 843-54.
26.	Hussain MS, Afzal O, Gupta G, et al. Unraveling NEAT1's complex role in lung cancer biology: a comprehensive review. EXCLI J, 2024, 23: 34-52.
27.	Zhu Q, Zhang C, Qu T, et al. MNX1-AS1 promotes phase separation of IGF2BP1 to drive c-Myc-mediated cell-cycle progression and proliferation in lung cancer. Cancer Res, 2022, 82(23): 4340-4358.
28.	Zhao MY, Wang LM, Liu J, et al. MiR-21 Suppresses anoikis through targeting PDCD4 and PTEN in human esophageal adenocarcinoma. Curr Med Sci, 2018, 38(2): 245-251.
29.	Liu C, Hu W, Li LL, et al. Roles of miR-200 family members in lung cancer: more than tumor suppressors. Future Oncol, 2018, 14(27): 2875-2886.
30.	Zhou H, Wang Y, Liu Z, et al. Recent advances of NEAT1-miRNA interactions in cancer. Acta Biochim Biophys Sin (Shanghai), 2022, 54(2): 153-162.
31.	Mu L, Zhao H, Yang Y, et al. Long noncoding RNA NEAT1 aggravates sorafenib-resistance in non-small cell lung cancer via regulating miRNA-335/c-Met. J BUON, 2021, 26(2): 345-352.
32.	Boyle ST, Poltavets V, Kular J, et al. ROCK-mediated selective activation of PERK signalling causes fibroblast reprogramming and tumour progression through a CRELD2-dependent mechanism. Nat Cell Biol, 2020, 22(7): 882-895.
33.	Yang Y, Li L, He H, et al. Numb inhibits migration and promotes proliferation of colon cancer cells via RhoA/ROCK signaling pathway repression. Exp Cell Res, 2022, 411(2): 113004.
34.	Zhao L, Ren C, Fang Y, et al. MiR-490-3p Sponged by lncRNA NEAT1 can attenuate lung adenocarcinoma progression by suppressing the RhoA/ROCK signaling pathway. Ann Clin Lab Sci, 2023, 53(1): 42-51.
35.	Zhang Y, Luo M, Cui X, et al. Long noncoding RNA NEAT1 promotes ferroptosis by modulating the miR-362-3p/MIOX axis as a ceRNA. Cell Death Differ, 2022, 29(9): 1850-1863.
36.	Xiong DD, Li ZY, Liang L, et al. The lncRNA NEAT1 accelerates lung adenocarcinoma deterioration and binds to Mir-193a-3p as a competitive endogenous RNA. Cell Physiol Biochem, 2018, 48(3): 905-918.
37.	Chen J, Liao X, Cheng J, et al. Targeted methylation of the LncRNA NEAT1 suppresses malignancy of renal cell carcinoma. Front Cell Dev Biol, 2021, 9: 777349.
38.	Lo PK, Zhang Y, Wolfson B, et al. Dysregulation of the BRCA1/long non-coding RNA NEAT1 signaling axis contributes to breast tumorigenesis. Oncotarget, 2016, 7(40): 65067-65089.
39.	Zakaria MA, Rajab NF, Chua EW, et al. Roles of Rho-associated kinase in lung cancer. Int J Oncol, 2021, 58(2): 185-198.
40.	Zhong Y, He JW, Huang CX, et al. The NcRNA/Wnt axis in lung cancer: oncogenic mechanisms, remarkable indicators and therapeutic targets. J Transl Med, 2025, 23(1): 326.
41.	Ali FEM, Badran KSA, El-Maksoud MSA, et al. The role of Wnt/β-catenin signaling in lung cancer progression and therapy: a comprehensive review. Med Oncol, 2025, 42(6): 183.
42.	Zhao L, Bi M, Zhang H, et al. Downregulation of NEAT1 Suppresses Cell Proliferation, migration, and invasion in NSCLC via sponging miR-153-3p. Cancer Biother Radiopharm, 2020, 35(5): 362-370.
43.	Yin L, Wang Y. Extracellular vesicles derived from M2-polarized tumor-associated macrophages promote immune escape in ovarian cancer through NEAT1/miR-101-3p/ZEB1/PD-L1 axis. Cancer Immunol Immunother, 2023, 72(3): 743-758.
44.	Kong X, Zhao Y, Li X, et al. Overexpression of HIF-2α-dependent NEAT1 promotes the progression of non-small cell lung cancer through miR-101-3p/SOX9/Wnt/β-catenin signal pathway. Cell Physiol Biochem, 2019, 52(3): 368-381.
45.	Lin W, Wang N, Wu S, et al. NUAK1-mediated phosphorylation of NADK mitigates ROS accumulation to promote osimertinib resistance in non-small cell lung carcinoma. Cancer Res, 2024, 84(23): 4081-4098.
46.	Zhao MM, Ge LY, Yang LF, et al. LncRNA NEAT1/miR-204/NUAK1 axis is a potential therapeutic target for non-small cell lung cancer. Cancer Manag Res, 2020, 12: 13357-13368.
47.	Zhu W, Wu C, Liu Z, et al. SULF1 regulates malignant progression of colorectal cancer by modulating ARSH via FAK/PI3K/AKT/mTOR signaling. Cancer Cell Int, 2024, 24(1): 201.
48.	Chen LM, Niu YD, Xiao M, et al. LncRNA NEAT1 regulated cell proliferation, invasion, migration and apoptosis by targeting has-miR-376b-3p/SULF1 axis in non-small cell lung cancer. Eur Rev Med Pharmacol Sci, 2020, 24(9): 4810-4821.
49.	Qi L, Yin Y, Sun M. m6A-mediated lncRNA NEAT1 plays an oncogenic role in non-small cell lung cancer by upregulating the HMGA1 expression through binding miR-361-3p. Genes Genomics, 2023, 45(12): 1537-1547.
50.	Zhen S, Jia Y, Zhao Y, et al. NEAT1_1 confers gefitinib resistance in lung adenocarcinoma through promoting AKR1C1-mediated ferroptosis defence. Cell Death Discov, 2024, 10(1): 131.
51.	Gu G, Hu C, Hui K, et al. NEAT 1 knockdown enhances the sensitivity of human non-small-cell lung cancer cells to anlotinib. Aging (Albany NY), 2021, 13(10): 13941-13953.

1. Smolarz B, ?ukasiewicz H, Samulak D, et al. Lung cancer-epidemiology, pathogenesis, treatment and molecular aspect (review of literature). Int J Mol Sci, 2025, 26(5): 2049.
2. Bouchard N, Daaboul N. Lung cancer: targeted therapy in 2025. Curr Oncol, 2025, 32(3): 146.
3. Jeon H, Wang S, Song J, et al. Update 2025: Management of non-small-cell lung cancer. Lung, 2025, 203(1): 53.
4. Zhang S, Guo J, He Y, et al. Roles of lncRNA in the crosstalk between osteogenesis and angiogenesis in the bone microenvironment. J Zhejiang Univ Sci B, 2025, 26(2): 107-123.
5. Suliman M, Saleh RO, Chandra M, et al. Macrophage-derived lncRNAs in cancer: regulators of tumor progression and therapeutic targets. Med Oncol, 2025, 42(4): 91.
6. Shi L, Li B, Tan J, et al. Exosomal lncRNA Mir100hg from lung cancer stem cells activates H3K14 lactylation to enhance metastatic activity in non-stem lung cancer cells. J Nanobiotechnology, 2025, 23(1): 156.
7. De Domenico S, La Banca V, D'Amico S, et al. Defining the transcriptional routes controlling lncRNA NEAT1 expression: implications in cellular stress response, inflammation, and differentiation. Discov Oncol, 2025, 16(1): 768.
8. Gu J, Wang Q, Mo J, et al. NEAT1 promotes the perineural invasion of pancreatic cancer via the E2F1/GDNF axis. Cancer Lett, 2025, 613: 217497.
9. Cheng N, Guo Y. Long Noncoding RNA NEAT1 Promotes Nasopharyngeal carcinoma progression through regulation of miR-124/NF-κB Pathway. Onco Targets Ther, 2023, 16: 639-640.
10. Chen D, Wang J, Li Y, et al. LncRNA NEAT1 suppresses cellular senescence in hepatocellular carcinoma via KIF11-dependent repression of CDKN2A. Clin Transl Med, 2023, 13(9): e1418.
11. Hu Z, Chen J, Meng P, et al. Association between NEAT1 polymorphism and the risk of lung cancer: A protocol for systematic review and meta-analysis. Medicine (Baltimore), 2021, 100(16): e25478.
12. Wang S, Cui Z, Li H, et al. LncRNA NEAT1 polymorphisms and lung cancer susceptibility in a Chinese Northeast Han Population: a case-control study. Pathol Res Pract, 2019, 215(12): 152723.
13. Wu YC, Ku MH, Huang WL, et al. NEAT1 in ovarian cancer: a key regulator of tumor progression, follicular fluid dynamics, and therapeutic resistance. Anticancer Res, 2025, 45(3): 825-842.
14. Zhang M, Weng W, Zhang Q, et al. The lncRNA NEAT1 activates Wnt/β-catenin signaling and promotes colorectal cancer progression via interacting with DDX5. J Hematol Oncol, 2018, 11(1): 113.
15. Skeparnias I, Zhang J. Structural basis of NEAT1 lncRNA maturation and menRNA instability. Nat Struct Mol Biol, 2024, 31(11): 1650-1654.
16. Hirose T, Yamazaki T, Nakagawa S. Molecular anatomy of the architectural NEAT1 noncoding RNA: The domains, interactors, and biogenesis pathway required to build phase-separated nuclear paraspeckles. Wiley Interdiscip Rev RNA, 2019, 10(6): e1545.
17. Weghorst F, Torres Marcén M, Faridi G, et al. Deep conservation and unexpected evolutionary history of neighboring lncRNAs MALAT1 and NEAT1. J Mol Evol, 2024, 92(1): 30-41.
18. Wu D, Li H, Wang J, et al. LncRNA NEAT1 promotes gastric cancer progression via miR-1294/AKT1 axis. Open Med (Wars), 2020 Oct 9;15(1): 1028-1038.
19. Zhang M, Guo J, Liu L, et al. The role of long non-coding RNA, nuclear enriched abundant transcript 1 (NEAT1) in cancer and other pathologies. Biochem Genet, 2022, 60(3): 843-867.
20. Fu X, Deng X, Xiao W, et al. Downregulation of NEAT1 sensitizes gemcitabine-resistant pancreatic cancer cells to gemcitabine through modulation of the miR-506-3p/ZEB2/EMT axis. Am J Cancer Res, 2021, 11(8): 3841-3856.
21. An Y, Huang F, Tan X, et al. Exosomes of adipose tissue-derived stem cells promote wound healing by sponging miR-17-5p and inducing autophagy protein Ulk1. Plast Reconstr Surg, 2023, 151(5): 1016-1028.
22. Sweef O, Mahfouz R, Ta?c?o?lu T, et al. Decoding lncRNA in COPD: unveiling prognostic and diagnostic power and their driving role in lung cancer progression. Int J Mol Sci, 2024, 25(16): 9001.
23. Kahraman DT, Bozgeyik E, Guven H, et al. Long non-coding RNA signatures in non-small cell lung cancer and their clinicopathological significance. Pathol Res Pract, 2024, 253: 154946.
24. Li Y, Zhou B, Yang Y, et al. Expression and clinical relevance of serum lncRNA NEAT1 and microRNA-31 in patients with advanced lung cancer and pulmonary infection. Altern Ther Health Med, 2024, 19: AT9614.
25. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell, 1993, 75(5): 843-54.
26. Hussain MS, Afzal O, Gupta G, et al. Unraveling NEAT1's complex role in lung cancer biology: a comprehensive review. EXCLI J, 2024, 23: 34-52.
27. Zhu Q, Zhang C, Qu T, et al. MNX1-AS1 promotes phase separation of IGF2BP1 to drive c-Myc-mediated cell-cycle progression and proliferation in lung cancer. Cancer Res, 2022, 82(23): 4340-4358.
28. Zhao MY, Wang LM, Liu J, et al. MiR-21 Suppresses anoikis through targeting PDCD4 and PTEN in human esophageal adenocarcinoma. Curr Med Sci, 2018, 38(2): 245-251.
29. Liu C, Hu W, Li LL, et al. Roles of miR-200 family members in lung cancer: more than tumor suppressors. Future Oncol, 2018, 14(27): 2875-2886.
30. Zhou H, Wang Y, Liu Z, et al. Recent advances of NEAT1-miRNA interactions in cancer. Acta Biochim Biophys Sin (Shanghai), 2022, 54(2): 153-162.
31. Mu L, Zhao H, Yang Y, et al. Long noncoding RNA NEAT1 aggravates sorafenib-resistance in non-small cell lung cancer via regulating miRNA-335/c-Met. J BUON, 2021, 26(2): 345-352.
32. Boyle ST, Poltavets V, Kular J, et al. ROCK-mediated selective activation of PERK signalling causes fibroblast reprogramming and tumour progression through a CRELD2-dependent mechanism. Nat Cell Biol, 2020, 22(7): 882-895.
33. Yang Y, Li L, He H, et al. Numb inhibits migration and promotes proliferation of colon cancer cells via RhoA/ROCK signaling pathway repression. Exp Cell Res, 2022, 411(2): 113004.
34. Zhao L, Ren C, Fang Y, et al. MiR-490-3p Sponged by lncRNA NEAT1 can attenuate lung adenocarcinoma progression by suppressing the RhoA/ROCK signaling pathway. Ann Clin Lab Sci, 2023, 53(1): 42-51.
35. Zhang Y, Luo M, Cui X, et al. Long noncoding RNA NEAT1 promotes ferroptosis by modulating the miR-362-3p/MIOX axis as a ceRNA. Cell Death Differ, 2022, 29(9): 1850-1863.
36. Xiong DD, Li ZY, Liang L, et al. The lncRNA NEAT1 accelerates lung adenocarcinoma deterioration and binds to Mir-193a-3p as a competitive endogenous RNA. Cell Physiol Biochem, 2018, 48(3): 905-918.
37. Chen J, Liao X, Cheng J, et al. Targeted methylation of the LncRNA NEAT1 suppresses malignancy of renal cell carcinoma. Front Cell Dev Biol, 2021, 9: 777349.
38. Lo PK, Zhang Y, Wolfson B, et al. Dysregulation of the BRCA1/long non-coding RNA NEAT1 signaling axis contributes to breast tumorigenesis. Oncotarget, 2016, 7(40): 65067-65089.
39. Zakaria MA, Rajab NF, Chua EW, et al. Roles of Rho-associated kinase in lung cancer. Int J Oncol, 2021, 58(2): 185-198.
40. Zhong Y, He JW, Huang CX, et al. The NcRNA/Wnt axis in lung cancer: oncogenic mechanisms, remarkable indicators and therapeutic targets. J Transl Med, 2025, 23(1): 326.
41. Ali FEM, Badran KSA, El-Maksoud MSA, et al. The role of Wnt/β-catenin signaling in lung cancer progression and therapy: a comprehensive review. Med Oncol, 2025, 42(6): 183.
42. Zhao L, Bi M, Zhang H, et al. Downregulation of NEAT1 Suppresses Cell Proliferation, migration, and invasion in NSCLC via sponging miR-153-3p. Cancer Biother Radiopharm, 2020, 35(5): 362-370.
43. Yin L, Wang Y. Extracellular vesicles derived from M2-polarized tumor-associated macrophages promote immune escape in ovarian cancer through NEAT1/miR-101-3p/ZEB1/PD-L1 axis. Cancer Immunol Immunother, 2023, 72(3): 743-758.
44. Kong X, Zhao Y, Li X, et al. Overexpression of HIF-2α-dependent NEAT1 promotes the progression of non-small cell lung cancer through miR-101-3p/SOX9/Wnt/β-catenin signal pathway. Cell Physiol Biochem, 2019, 52(3): 368-381.
45. Lin W, Wang N, Wu S, et al. NUAK1-mediated phosphorylation of NADK mitigates ROS accumulation to promote osimertinib resistance in non-small cell lung carcinoma. Cancer Res, 2024, 84(23): 4081-4098.
46. Zhao MM, Ge LY, Yang LF, et al. LncRNA NEAT1/miR-204/NUAK1 axis is a potential therapeutic target for non-small cell lung cancer. Cancer Manag Res, 2020, 12: 13357-13368.
47. Zhu W, Wu C, Liu Z, et al. SULF1 regulates malignant progression of colorectal cancer by modulating ARSH via FAK/PI3K/AKT/mTOR signaling. Cancer Cell Int, 2024, 24(1): 201.
48. Chen LM, Niu YD, Xiao M, et al. LncRNA NEAT1 regulated cell proliferation, invasion, migration and apoptosis by targeting has-miR-376b-3p/SULF1 axis in non-small cell lung cancer. Eur Rev Med Pharmacol Sci, 2020, 24(9): 4810-4821.
49. Qi L, Yin Y, Sun M. m6A-mediated lncRNA NEAT1 plays an oncogenic role in non-small cell lung cancer by upregulating the HMGA1 expression through binding miR-361-3p. Genes Genomics, 2023, 45(12): 1537-1547.
50. Zhen S, Jia Y, Zhao Y, et al. NEAT1_1 confers gefitinib resistance in lung adenocarcinoma through promoting AKR1C1-mediated ferroptosis defence. Cell Death Discov, 2024, 10(1): 131.
51. Gu G, Hu C, Hui K, et al. NEAT 1 knockdown enhances the sensitivity of human non-small-cell lung cancer cells to anlotinib. Aging (Albany NY), 2021, 13(10): 13941-13953.

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NEAT1調控miRNA在肺癌中作用機制研究進展

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