Long non coding RNA SNHG4 promotes proliferation, apoptosis, migration, and invasion of non-small cell lung cancer cells by regulating the miR-409-3p/DDX5 signaling axis_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

LIU Xiaoping ^1,2 ,  YANG Yanxia ^1,2 , CHEN Keyi ^2,3 , YANG Xue ^2,3 , KE Xiaoxian ^2,3 , LI Kaikai ^2,3 , LI Shuhua ^1,2 , WANG Xin ^1,2 , MA Xueping ^1,2 , WEI Suzhen ^1,2

1. The Second Hospital of Gansu Province, Lanzhou, Gansu 730000, P.R.China;
2. Affiliated Hospital of Northwest Minzu University, Lanzhou, Gansu 730000, P.R.China;
3. School of Clinical Medicine Northwest Minzu University, Lanzhou, Gansu 730000, P.R.China;

Corresponding?author：

YANG Yanxia, Email: 497534365@qq.com

Keywords：

Non-small cell lung cancer; long non coding RNA SNHG4; miR-409-3p; DDX5

DOI：

10.7507/1671-6205.202412067

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Objective This study aimed to identify long non-coding RNAs (lncRNAs) that could serve as prognostic biomarkers for non-small cell lung cancer (NSCLC).Methods The Encyclopedia of RNA Interactomes (ENCORI) database was used to analyze the expression profile and RNA interaction network of lncRNA SNHG4 in NSCLC. Cell experiments were performed to determine the effects of lncRNA SNHG4 on the proliferation and migration of lung cancer cell line A549. The dual-luciferase reporter assay was employed to validate the interaction between SNHG4 and its potential targets.Results lncRNA SNHG4 was highly expressed in NSCLC tissues. Kaplan-Meier survival analysis showed that patient survival rate was significantly correlated with SNHG4 expression levels. Knockdown of SNHG4 inhibited the proliferation, migration, and invasion of NSCLC cells while promoting cell apoptosis. Mechanistic studies identified miR-409-3p and DDX5 as direct targets of SNHG4. SNHG4 downregulated miR-409-3p expression in NSCLC cells, thereby relieving the inhibitory effect of miR-409-3p on DDX5 and promoting NSCLC cell growth. Conclusion lncRNA SNHG4 may exert its tumor-promoting role in NSCLC through the lncRNA SNHG4/miR-409-3p/DDX5 signaling pathway.

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2.	Mattick JS, Amaral PP, Carninci P, et al. Long non-coding RNAs: definitions, functions, challenges and recommendations. Nat Rev Mol Cell Biol, 2023, 24(6): 430-447.
3.	Chodurska B, Kunej T. Long non-coding RNAs in humans: Classification, genomic organization and function. Noncoding RNA Res, 2025, 11: 313-327.
4.	Nandwani A, Rathore S, Datta M. LncRNAs in cancer: Regulatory and therapeutic implications. Cancer Lett, 2021, 501: 162-171.
5.	Wang L, Cho KB, Li Y, et al. Long Noncoding RNA (lncRNA)-Mediated Competing Endogenous RNA Networks Provide Novel Potential Biomarkers and Therapeutic Targets for Colorectal Cancer. Int J Mol Sci, 2019, 20(22): 5758.
6.	Zhang T, Wu D, Li Z, et al. The roles of the small nucleolar RNA host gene family in ovarian cancer. Cancer Biol Ther, 2025, 26(1): 2574773.
7.	Li JH, Liu S, Zhou H, Qu LH, Yang JH. starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res, 2014, 42(Database issue): D92-D97.
8.	吳瓊,汪玉蘭,趙健,等. 癌癥中lncRNA調控可變剪接的生物信息學研究進展. 生物信息學, 2024, 22(4): 239-251.
9.	Pourghasem N, Ghorbanzadeh S, Nejatizadeh AA. The Regulatory Mechanisms and Clinical Significance of Lnc SNHG4 in Cancer. Curr Pharm Des. 2022, 28(44): 3563-3571.
10.	Dong Q, Qiu H, Piao C, Li Z, Cui X. LncRNA SNHG4 promotes prostate cancer cell survival and resistance to enzalutamide through a let-7a/RREB1 positive feedback loop and a ceRNA network. J Exp Clin Cancer Res. 2023, 42(1): 209.
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12.	Zhou N, Chen Y, Yang L, et al. LncRNA SNHG4 promotes malignant biological behaviors and immune escape of colorectal cancer cells by regulating the miR-144-3p/MET axis. Am J Transl Res. 2021, 13(10): 11144-11161.
13.	Wang S, Zhu W, Qiu J, Chen F. lncRNA SNHG4 promotes cell proliferation, migration, invasion and the epithelial-mesenchymal transition process via sponging miR-204-5p in gastric cancer. Mol Med Rep. 2021, 23(1): 85.
14.	Qiu J, Wang P, Chen Z, et al. Long noncoding RNA SNHG4 promotes the malignant progression of hepatocellular carcinoma through the miR-211-5p/CREB5 axis. Cancer Med. 2023, 12(7): 8388-8402.
15.	Li Z, Zhuo Y, Li J, Zhang M, Wang R, Lin L. Long Non-Coding RNA SNHG4 Is a Potential Diagnostic and Prognostic Indicator in Non-Small Cell Lung Cancer. Ann Clin Lab Sci. 2021, 51(5): 654-662.
16.	Ghafouri-Fard S, Shoorei H, Branicki W, Taheri M. Non-coding RNA profile in lung cancer. Exp Mol Pathol. 2020, 114: 104411.
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18.	Pooresmaeil F, Azadi S, Hasannejad-Asl B, Takamoli S, Bolhassani A. Pivotal Role of miRNA-lncRNA Interactions in Human Diseases. Mol Biotechnol. 2025, 67(12): 4363-4385.
19.	Elimam H, Radwan AF, El Said NH, et al. Long non-coding RNAs and signaling networks in non-small cell lung cancer: mechanistic insights into tumor pathogenesis. Cancer Gene Ther. 2025, 32(11): 1145-1165.
20.	Sun Q, Hao Q, Prasanth KV. Nuclear Long Noncoding RNAs: Key Regulators of Gene Expression. Trends Genet. 2018, 34(2): 142-157.
21.	Long Y, Wang X, Youmans DT, Cech TR. How do lncRNAs regulate transcription?. Sci Adv. 2017, 3(9): eaao2110.
22.	He RZ, Luo DX, Mo YY. Emerging roles of lncRNAs in the post-transcriptional regulation in cancer. Genes Dis. 2019, 6(1): 6-15.
23.	Liang X, Wang X. LncRNAs: Current understanding, future directions, and challenges. Animal Model Exp Med. 2023, 6(6): 505-507.
24.	Luo S, Lu JY, Liu L, et al. Divergent lncRNAs Regulate Gene Expression and Lineage Differentiation in Pluripotent Cells. Cell Stem Cell. 2016, 18(5): 637-652.
25.	Nyamao RM, Wu J, Yu L, Xiao X, Zhang FM. Roles of DDX5 in the tumorigenesis, proliferation, differentiation, metastasis and pathway regulation of human malignancies. Biochim Biophys Acta Rev Cancer. 2019, 1871(1): 85-98.
26.	Li Y, Liu X, Cui X, et al. LncRNA PRADX-mediated recruitment of PRC2/DDX5 complex suppresses UBXN1 expression and activates NF-κB activity, promoting tumorigenesis. Theranostics. 2021, 11(9): 4516-4530.
27.	Hashemi V, Masjedi A, Hazhir-Karzar B, et al. The role of DEAD-box RNA helicase p68 (DDX5) in the development and treatment of breast cancer. J Cell Physiol. 2019, 234(5): 5478-5487.
28.	Ma Z, Feng J, Guo Y, et al. Knockdown of DDX5 Inhibits the Proliferation and Tumorigenesis in Esophageal Cancer. Oncol Res. 2017, 25(6): 887-895.
29.	Xu K, Sun S, Yan M, et al. DDX5 and DDX17-multifaceted proteins in the regulation of tumorigenesis and tumor progression. Front Oncol, 2022, 12: 943032.
30.	Le TK, Cherif C, Omabe K, et al. DDX5 mRNA-targeting antisense oligonucleotide as a new promising therapeutic in combating castration-resistant prostate cancer. Mol Ther. 2023, 31(2): 471-486.

1. Tan YT, Lin JF, Li T, et al. LncRNA-mediated posttranslational modifications and reprogramming of energy metabolism in cancer. Cancer Commun (Lond), 2021, 41(2): 109-120.
2. Mattick JS, Amaral PP, Carninci P, et al. Long non-coding RNAs: definitions, functions, challenges and recommendations. Nat Rev Mol Cell Biol, 2023, 24(6): 430-447.
3. Chodurska B, Kunej T. Long non-coding RNAs in humans: Classification, genomic organization and function. Noncoding RNA Res, 2025, 11: 313-327.
4. Nandwani A, Rathore S, Datta M. LncRNAs in cancer: Regulatory and therapeutic implications. Cancer Lett, 2021, 501: 162-171.
5. Wang L, Cho KB, Li Y, et al. Long Noncoding RNA (lncRNA)-Mediated Competing Endogenous RNA Networks Provide Novel Potential Biomarkers and Therapeutic Targets for Colorectal Cancer. Int J Mol Sci, 2019, 20(22): 5758.
6. Zhang T, Wu D, Li Z, et al. The roles of the small nucleolar RNA host gene family in ovarian cancer. Cancer Biol Ther, 2025, 26(1): 2574773.
7. Li JH, Liu S, Zhou H, Qu LH, Yang JH. starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res, 2014, 42(Database issue): D92-D97.
8. 吳瓊,汪玉蘭,趙健,等. 癌癥中lncRNA調控可變剪接的生物信息學研究進展. 生物信息學, 2024, 22(4): 239-251.
9. Pourghasem N, Ghorbanzadeh S, Nejatizadeh AA. The Regulatory Mechanisms and Clinical Significance of Lnc SNHG4 in Cancer. Curr Pharm Des. 2022, 28(44): 3563-3571.
10. Dong Q, Qiu H, Piao C, Li Z, Cui X. LncRNA SNHG4 promotes prostate cancer cell survival and resistance to enzalutamide through a let-7a/RREB1 positive feedback loop and a ceRNA network. J Exp Clin Cancer Res. 2023, 42(1): 209.
11. Chu Q, Gu X, Zheng Q, et al. Long noncoding RNA SNHG4: a novel target in human diseases. Cancer Cell Int. 2021, 21(1): 583.
12. Zhou N, Chen Y, Yang L, et al. LncRNA SNHG4 promotes malignant biological behaviors and immune escape of colorectal cancer cells by regulating the miR-144-3p/MET axis. Am J Transl Res. 2021, 13(10): 11144-11161.
13. Wang S, Zhu W, Qiu J, Chen F. lncRNA SNHG4 promotes cell proliferation, migration, invasion and the epithelial-mesenchymal transition process via sponging miR-204-5p in gastric cancer. Mol Med Rep. 2021, 23(1): 85.
14. Qiu J, Wang P, Chen Z, et al. Long noncoding RNA SNHG4 promotes the malignant progression of hepatocellular carcinoma through the miR-211-5p/CREB5 axis. Cancer Med. 2023, 12(7): 8388-8402.
15. Li Z, Zhuo Y, Li J, Zhang M, Wang R, Lin L. Long Non-Coding RNA SNHG4 Is a Potential Diagnostic and Prognostic Indicator in Non-Small Cell Lung Cancer. Ann Clin Lab Sci. 2021, 51(5): 654-662.
16. Ghafouri-Fard S, Shoorei H, Branicki W, Taheri M. Non-coding RNA profile in lung cancer. Exp Mol Pathol. 2020, 114: 104411.
17. Kadian LK, Verma D, Lohani N, et al. Long non-coding RNAs in cancer: multifaceted roles and potential targets for immunotherapy. Mol Cell Biochem. 2024, 479(12): 3229-3254.
18. Pooresmaeil F, Azadi S, Hasannejad-Asl B, Takamoli S, Bolhassani A. Pivotal Role of miRNA-lncRNA Interactions in Human Diseases. Mol Biotechnol. 2025, 67(12): 4363-4385.
19. Elimam H, Radwan AF, El Said NH, et al. Long non-coding RNAs and signaling networks in non-small cell lung cancer: mechanistic insights into tumor pathogenesis. Cancer Gene Ther. 2025, 32(11): 1145-1165.
20. Sun Q, Hao Q, Prasanth KV. Nuclear Long Noncoding RNAs: Key Regulators of Gene Expression. Trends Genet. 2018, 34(2): 142-157.
21. Long Y, Wang X, Youmans DT, Cech TR. How do lncRNAs regulate transcription?. Sci Adv. 2017, 3(9): eaao2110.
22. He RZ, Luo DX, Mo YY. Emerging roles of lncRNAs in the post-transcriptional regulation in cancer. Genes Dis. 2019, 6(1): 6-15.
23. Liang X, Wang X. LncRNAs: Current understanding, future directions, and challenges. Animal Model Exp Med. 2023, 6(6): 505-507.
24. Luo S, Lu JY, Liu L, et al. Divergent lncRNAs Regulate Gene Expression and Lineage Differentiation in Pluripotent Cells. Cell Stem Cell. 2016, 18(5): 637-652.
25. Nyamao RM, Wu J, Yu L, Xiao X, Zhang FM. Roles of DDX5 in the tumorigenesis, proliferation, differentiation, metastasis and pathway regulation of human malignancies. Biochim Biophys Acta Rev Cancer. 2019, 1871(1): 85-98.
26. Li Y, Liu X, Cui X, et al. LncRNA PRADX-mediated recruitment of PRC2/DDX5 complex suppresses UBXN1 expression and activates NF-κB activity, promoting tumorigenesis. Theranostics. 2021, 11(9): 4516-4530.
27. Hashemi V, Masjedi A, Hazhir-Karzar B, et al. The role of DEAD-box RNA helicase p68 (DDX5) in the development and treatment of breast cancer. J Cell Physiol. 2019, 234(5): 5478-5487.
28. Ma Z, Feng J, Guo Y, et al. Knockdown of DDX5 Inhibits the Proliferation and Tumorigenesis in Esophageal Cancer. Oncol Res. 2017, 25(6): 887-895.
29. Xu K, Sun S, Yan M, et al. DDX5 and DDX17-multifaceted proteins in the regulation of tumorigenesis and tumor progression. Front Oncol, 2022, 12: 943032.
30. Le TK, Cherif C, Omabe K, et al. DDX5 mRNA-targeting antisense oligonucleotide as a new promising therapeutic in combating castration-resistant prostate cancer. Mol Ther. 2023, 31(2): 471-486.

Chinese Journal of Respiratory and Critical Care Medicine

Latest ArticlesLong non coding RNA SNHG4 promotes proliferation, apoptosis, migration, and invasion of non-small cell lung cancer cells by regulating the miR-409-3p/DDX5 signaling axis

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