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The role of LncRNA-MANCR induced by HIF-1α drive the malignant progression of pancreatic cancer by targeting miRNA-494/SIRT1 signaling axis under hypoxic conditions

Cancer Gene Therapy volume 32, pages 633–648 (2025)Cite this article

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Abstract

This study revealed the prospective biological role and fundamental mechanisms of hypoxia-induced lncRNA-MANCR (MANCR), which is notably upregulated in pancreatic cancer (PC). This work uncovered the potential biological function and underlying mechanisms of hypoxia-induced MANCR, which is significantly elevated in PC. Microarray assays confirmed MANCR expression in the tissues of patients with PC and patients with chronic pancreatitis (CP), which positively correlated with sirtuin-1 (SIRT1) mRNA levels. Chromatin immunoprecipitation and luciferase assays were employed to gauge binding within the hypoxia-inducible factor-1α (HIF-1α)/MANCR/miRNA-494/SIRT1 pathway. Additionally, the association between MANCR expression and the clinical outcomes of patients with PC was confirmed. MANCR is significantly upregulated in PC cells under hypoxic conditions, which is closely linked to poor prognosis in patients with PC. Depletion of MANCR repressed in vitro proliferation, migration, and invasion of PC cells and in vivo growth of PC xenograft tumours. We further demonstrated that MANCR is localised in the cytoplasm and competitively binds miR-494, which directly targets SIRT1. Mechanically, the overexpression of SIRT1 improved the stability of the HIF-1α protein through deacetylation, leading to enhanced HIF-1α assembly. Moreover, MANCR underwent transcriptional regulation by HIF-1α in a hypoxic setting. This modulation was ascribed to HIF-1α binding to hypoxia response elements present in the MANCR promoter sequence. Data revealed the potential possibility of feedback between MANCR and HIF-1α, which may be conducive to hypoxia-induced oncogenicity and PC tumorigenesis, thereby providing a suitable therapeutic target.

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Fig. 1: The lncRNA-MANCR is overexpressed in pancreatic cancer and chronic pancreatitis tissues, which correlates with poor clinical results.
Fig. 2: The lncRNA-MANCR facilitates the invasion and proliferation of pancreatic cancer cells, and is accompanied by increased SIRT1 expression.
Fig. 3: The lncRNA-MANCR regulates SIRT1 expression via competitive binding with miR-494.
Fig. 4: Inhibition of miR-494 reverses the suppressing effect of LV-MANCR-siRNA in PC cells.
Fig. 5: Both downregulated LV-MANCR and overexpressed miR-494 suppress tumour growth and metastasis in vivo.
Fig. 6: Hypoxia induces overexpression of lncRNA-MANCR expression in a HIF-1α-mediated manner.
Fig. 7: The lncRNA-MANCR enhances HIF-1α expression by SIRT1-dependent deacetylation.
Fig. 8: Correlation between MANCR, SIRT1, and HIF-1α expression in PC samples.

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Upon reasonable request, the corresponding authors will provide all data that supports the findings of this study.

References

  1. Halbrook CJ, Lyssiotis CA, Pasca di Magliano M, Maitra A. Pancreatic cancer: Advances and challenges. Cell. 2023;186:1729–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021;71:7–33.

    Article  PubMed  Google Scholar 

  3. Wood LD, Canto MI, Jaffee EM, Simeone DM. Pancreatic Cancer: Pathogenesis, Screening, Diagnosis, and Treatment. Gastroenterology. 2022;163:386–402.e1.

    Article  PubMed  Google Scholar 

  4. Duan H, Li L, He S. Advances and Prospects in the Treatment of Pancreatic Cancer. Int J Nanomed. 2023;18:3973–88.

    Article  CAS  Google Scholar 

  5. He Z, Wang J, Zhu C, Xu J, Chen P, Jiang X, et al. Exosome-derived FGD5-AS1 promotes tumor-associated macrophage M2 polarization-mediated pancreatic cancer cell proliferation and metastasis. Cancer Lett. 2022;548:215751.

    Article  CAS  PubMed  Google Scholar 

  6. Zhang Y, Liu X, Wang Y, Lai S, Wang Z, Yang Y, et al. The m6A demethylase ALKBH5-mediated upregulation of DDIT4-AS1 maintains pancreatic cancer stemness and suppresses chemosensitivity by activating the mTOR pathway. Mol Cancer. 2022;21:174.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Cave DD, Buonaiuto S, Sainz B Jr, Fantuz M, Mangini M, Carrer A, et al. LAMC2 marks a tumor-initiating cell population with an aggressive signature in pancreatic cancer. J Exp Clin Cancer Res. 2022;41:315.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Fatica A, Bozzoni I. Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet. 2014;15:7–21.

    Article  CAS  PubMed  Google Scholar 

  9. Wang J, He Z, Liu X, Xu J, Jiang X, Quan G, et al. LINC00941 promotes pancreatic cancer malignancy by interacting with ANXA2 and suppressing NEDD4L-mediated degradation of ANXA2. Cell Death Dis. 2022;13:718.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Zhou M, Pan S, Qin T, Zhao C, Yin T, Gao Y, et al. LncRNA FAM83H-AS1 promotes the malignant progression of pancreatic ductal adenocarcinoma by stabilizing FAM83H mRNA to protect β-catenin from degradation. J Exp Clin Cancer Res. 2022;41:288.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Jiang F, Li S, Wang X, Deng Y, Peng S. DPP10-AS1-mediated downregulation of MicroRNA-324-3p Is conducive to the malignancy of pancreatic cancer by enhancing CLDN3 Expression. Pancreas. 2022;51:1201–10.

    Article  CAS  PubMed  Google Scholar 

  12. Terashima M, Ishimura A, Wanna-Udom S, Suzuki T. MEG8 long noncoding RNA contributes to epigenetic progression of the epithelial-mesenchymal transition of lung and pancreatic cancer cells. J Biol Chem. 2018;293:18016–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Xu F, Huang M, Chen Q, Niu Y, Hu Y, Hu P, et al. LncRNA HIF1A-AS1 promotes gemcitabine resistance of pancreatic cancer by enhancing glycolysis through modulating the AKT/YB1/HIF1a pathway. Cancer Res. 2021;81:5678–91.

    Article  CAS  PubMed  Google Scholar 

  14. Liu Y, Shi M, He X, Cao Y, Liu P, Li F, et al. LncRNA-PACERR induces pro-tumour macrophages via interacting with miR-671-3p and m6A-reader IGF2BP2 in pancreatic ductal adenocarcinoma. J Hematol Oncol. 2022;15:52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Qiu X, Shi Q, Zhang X, Shi X, Jiang H, Qin S. LncRNA A2M-AS1 promotes ferroptosis in pancreatic cancer via interacting with PCBP3. Mol Cancer Res. 2022;20:1636–45.

    Article  CAS  PubMed  Google Scholar 

  16. Li X, Deng SJ, Zhu S, Jin Y, Cui SP, Chen JY, et al. Hypoxia-induced lncRNA-NUTF2P3-001 contributes to tumorigenesis of pancreatic cancer by derepressing the miR-3923/KRAS pathway. Oncotarget. 2016;7:6000–14.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Jin Y, Zhang Z, Yu Q, Zeng Z, Song H, Huang X, et al. Positive reciprocal feedback of lncRNA ZEB1-AS1 and HIF-1α contributes to hypoxia-promoted tumorigenesis and metastasis of pancreatic cancer. Front Oncol. 2021;11:761979.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Hinshaw DC, Shevde LA. The tumor microenvironment innately modulates cancer progression. Cancer Res. 2019;79:4557–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Jung HY, Fattet L, Yang J. Molecular pathways: linking tumor microenvironment to epithelial-mesenchymal transition in metastasis. Clin Cancer Res. 2015;21:962–8.

    Article  CAS  PubMed  Google Scholar 

  20. Jing X, Yang F, Shao C, Wei K, Xie M, Shen H, et al. Role of hypoxia in cancer therapy by regulating the tumor microenvironment. Mol Cancer. 2019;18:157.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Tao J, Yang G, Zhou W, Qiu J, Chen G, Luo W, et al. Targeting hypoxic tumor microenvironment in pancreatic cancer. J Hematol Oncol. 2021;14:14.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Liu M, Zhong J, Zeng Z, Huang K, Ye Z, Deng S, et al. Hypoxia-induced feedback of HIF-1a and lncRNA-CF129 contributes to pancreatic cancer progression through stabilization of p53 protein. Theranostics. 2019;9:4795–810.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Niu Y, Jin Y, Deng SC, Deng SJ, Zhu S, Liu Y, et al. MiRNA-646-mediated reciprocal repression between HIF-1a and MIIP contributes to tumorigenesis of pancreatic cancer. Oncogene. 2018;37:1743–58.

    Article  CAS  PubMed  Google Scholar 

  24. Deng S, Li X, Niu Y, Zhu S, Jin Y, Deng S, et al. MiR-652 inhibits acidic microenvironment induced epithelial-mesenchymal transition of pancreatic cancer cells by targeting ZEB1. Oncotarget. 2015;6:39661–75.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Zhu S, Zhou HY, Deng SC, Deng SJ, He C, Li X, et al. ASIC1 and ASIC3 contribute to acidity-induced EMT of pancreatic cancer through activating Ca2+/RhoA pathway. Cell Death Dis. 2017;8: e2806 https://doi.org/10.1038/cddis.2017.189.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Pastushenko I, Blanpain C. EMT transition states during tumor progression and metastasis. Trends Cell Biol. 2019;29:212–26.

    Article  CAS  PubMed  Google Scholar 

  27. Brabletz S, Schuhwerk H, Brabletz T, Stemmler MP. Dynamic EMT: a multi-tool for tumor progression. EMBO J. 2021;40:e108647.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Choupani J, Mansoori Derakhshan S, Bayat S, Alivand MR, Shekari Khaniani M. Narrower insight to SIRT1 role in cancer: A potential therapeutic target to control epithelial-mesenchymal transition in cancer cells. J Cell Physiol. 2018;233:4443–57.

    Article  CAS  PubMed  Google Scholar 

  29. Palmirotta R, Cives M, Della-Morte D, Capuani B, Lauro D, Guadagni F, et al. Sirtuins and cancer: role in the epithelial-mesenchymal transition. Oxid Med Cell Longev. 2016;2016. 3031459.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Deng S, Zhu S, Wang B, Li X, Liu Y, Qin Q, et al. Chronic pancreatitis and pancreatic cancer demonstrate active epithelial-mesenchymal transition profile, regulated by miR-217-SIRT1 pathway. Cancer Lett. 2014;355:184–91.

    Article  CAS  PubMed  Google Scholar 

  31. Zhou L, Jiang J, Huang Z, Jin P, Peng L, Luo M, et al. Hypoxia-induced lncRNA STEAP3-AS1 activates Wnt/β-catenin signaling to promote colorectal cancer progression by preventing m6A-mediated degradation of STEAP3 mRNA. Mol Cancer. 2022;21:168.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Li X, Yang J, Ni R, Chen J, Zhou Y, Song H, et al. Hypoxia-induced lncRNA RBM5-AS1 promotes tumorigenesis via activating Wnt/β-catenin signaling in breast cancer. Cell Death Dis. 2022;13:95.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Huang J, Zheng W, Zhang P, Lin Q, Chen Z, Xuan J, et al. ChIPBase v3.0: the encyclopedia of transcriptional regulations of non-coding RNAs and protein-coding genes. Nucleic Acids Res. 2023;51:D46–D56.

    Article  CAS  PubMed  Google Scholar 

  34. Yao L, Yan J, Gan L, Huang S, Cheng F, Fang N. Upregulation of MANCR predicts poor survival in patients with gastric cancer. Oncol Lett. 2019;18:6801–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Nagasawa M, Tomimatsu K, Terada K, Kondo K, Miyazaki K, Miyazaki M, et al. Long non-coding RNA MANCR is a target of BET bromodomain protein BRD4 and plays a critical role in cellular migration and invasion abilities of prostate cancer. Biochem Biophys Res Commun. 2020;526:128–34.

    Article  CAS  PubMed  Google Scholar 

  36. Tahmouresi F, Razmara E, Pakravan K, Mossahebi-Mohammadi M, Rouhollah F, Montazeri M, et al. Upregulation of the long noncoding RNAs DSCAM-AS1 and MANCR is a potential diagnostic marker for breast carcinoma. Biotechnol Appl Biochem. 2021;68:1250–6.

    CAS  PubMed  Google Scholar 

  37. Liu C, Li H, Li X, Zhao X, Zhang X. LncRNA MANCR positively affects the malignant progression of lung adenocarcinoma. BMC Pulm Med. 2021;21:272.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Jung JG, Le A. Metabolism of immune cells in the tumor microenvironment. Adv Exp Med Biol. 2021;1311:173–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Li J, Eu JQ, Kong LR, Wang L, Lim YC, Goh BC, et al. Targeting metabolism in cancer cells and the tumour microenvironment for cancer therapy. Molecules. 2020;25:4831.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Singleton DC, Macann A, Wilson WR. Therapeutic targeting of the hypoxic tumour microenvironment. Nat Rev Clin Oncol. 2021;18:751–72.

    Article  PubMed  Google Scholar 

  41. Wei X, Chen Y, Jiang X, Peng M, Liu Y, Mo Y, et al. Mechanisms of vasculogenic mimicry in hypoxic tumor microenvironments. Mol Cancer. 2021;20:7.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Tan Z, Xu J, Zhang B, Shi S, Yu X, Liang C. Hypoxia: a barricade to conquer the pancreatic cancer. Cell Mol Life Sci. 2020;77:3077–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Hua Q, Mi B, Xu F, Wen J, Zhao L, Liu J, et al. Hypoxia-induced lncRNA-AC020978 promotes proliferation and glycolytic metabolism of non-small cell lung cancer by regulating PKM2/HIF-1a axis. Theranostics. 2020;10:4762–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Carmeliet P, Dor Y, Herbert JM, Fukumura D, Brusselmans K, Dewerchin M, et al. Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature. 1998;394:485–90.

    Article  CAS  PubMed  Google Scholar 

  45. Sokkar P, Sathis V, Ramachandran M. Computational modeling on the recognition of the HRE motif by HIF-1: molecular docking and molecular dynamics studies. J Mol Model. 2012;18:1691–700.

    Article  CAS  PubMed  Google Scholar 

  46. Maxwell PH, Wiesener MS, Chang GW, Clifford SC, Vaux EC, Cockman ME, et al. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature. 1999;399:271–5.

    Article  CAS  PubMed  Google Scholar 

  47. Jeong JW, Bae MK, Ahn MY, Kim SH, Sohn TK, Bae MH, et al. Regulation and destabilization of HIF-1alpha by ARD1-mediated acetylation. Cell. 2002;111:709–20.

    Article  CAS  PubMed  Google Scholar 

  48. Kim SH, Jeong JW, Park JA, Lee JW, Seo JH, Jung BK, et al. Regulation of the HIF-1alpha stability by histone deacetylases. Oncol Rep. 2007;17:647–51.

  49. Jiang Y, Luo Z, Gong Y, Fu Y, Luo Y. NAD+ supplementation limits triple-negative breast cancer metastasis via SIRT1-P66Shc signaling. Oncogene. 2023;42:808–24.

    Article  CAS  PubMed  Google Scholar 

  50. Xie M, Liu M, He CS. SIRT1 regulates endothelial Notch signaling in lung cancer. PLoS One. 2012;7:e45331.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Yang D, Zhang P, Yang Z, Hou G, Yang Z. miR-4461 inhibits liver cancer stem cells expansion and chemoresistance via regulating SIRT1. Carcinogenesis. 2024;45:463–74.

    Article  CAS  PubMed  Google Scholar 

  52. Yu L, Dong L, Li H, Liu Z, Luo Z, Duan G, et al. Ubiquitination-mediated degradation of SIRT1 by SMURF2 suppresses CRC cell proliferation and tumorigenesis. Oncogene. 2020;39:4450–64.

    Article  CAS  PubMed  Google Scholar 

  53. Huang J, Zhang F, Hu G, Pan Y, Sun W, Jiang L, et al. SIRT1 suppresses pituitary tumor progression by downregulating PTTG1 expression. Oncol Rep. 2022;48:143.

    Article  CAS  PubMed  Google Scholar 

  54. Dilmac S, Kuscu N, Caner A, Yildirim S, Yoldas B, Farooqi AA, et al. SIRT1/FOXO signaling pathway in breast cancer progression and metastasis. Int J Mol Sci. 2022;23:10227.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Leng S, Huang W, Chen Y, Yang Y, Feng D, Liu W, et al. SIRT1 coordinates with the CRL4B complex to regulate pancreatic cancer stem cells to promote tumorigenesis. Cell Death Differ. 2021;28:3329–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Lim JH, Lee YM, Chun YS, Chen J, Kim JE, Park JW. Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor 1alpha. Mol Cell. 2010;38:864–78.

    Article  CAS  PubMed  Google Scholar 

  57. Joo HY, Yun M, Jeong J, Park ER, Shin HJ, Woo SR, et al. SIRT1 deacetylates and stabilizes hypoxia-inducible factor-1a (HIF-1a) via direct interactions during hypoxia. Biochem Biophys Res Commun. 2015;462:294–300.

    Article  CAS  PubMed  Google Scholar 

  58. Xue ST, Zheng B, Cao SQ, Ding JC, Hu GS, Liu W, et al. Long non-coding RNA LINC00680 functions as a ceRNA to promote esophageal squamous cell carcinoma progression through the miR-423-5p/PAK6 axis. Mol Cancer. 2022;21:69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Song YX, Sun JX, Zhao JH, Yang YC, Shi JX, Wu ZH, et al. Non-coding RNAs participate in the regulatory network of CLDN4 via ceRNA-mediated miRNA evasion. Nat Commun. 2017;8:289.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Liu Y, Li X, Zhu S, Zhang JG, Yang M, Qin Q, et al. Ectopic expression of miR-494 inhibited the proliferation, invasion and chemoresistance of pancreatic cancer by regulating SIRT1 and c-Myc. Gene Ther. 2015;22:729–38.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Not applicable.

Funding

This study was funded by National Natural Science Foundation of China (NO. 82370651, NO. 82070657, NO. 81902515), University Natural Science Research Project of Anhui Province (NO. 2024AH051959 and NO. KJ2019A0412), AnHui Province Educational Natural Science Project (2023AH040254) and Key Science Foundation of Wannan medical college (WK2023ZZD26 and WK2023ZZD25).

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  1. These authors contributed equally: Yan Jin, Hao Hu, Yitong Tian.

Authors and Affiliations

  1. Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China

    Yan Jin, Long Cheng, Xiaoyu Guo & Gang Wang

  2. Department of Gastrointestinal Surgery, The First Affiliated Yijishan Hospital of Wannan Medical College, Wuhu, Anhui Province, China

    Yan Jin, Hao Hu & Xiaoxu Huang

  3. Oncological and Laparoscopic Surgery Department, The First Affiliated Hospital of Harbin Medical University, Harbin, China

    Yan Jin, Long Cheng, Xiaoyu Guo & Gang Wang

  4. Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, China

    Yitong Tian

  5. Department of Radiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

    Han Xu

  6. Ultrasound medicine department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China

    Qiao Yu

  7. School of Medicine, Stanford University, San Francisco, CA, USA

    Zongwei Wang

  8. Department of Hepatobiliary Surgery, The First Affiliated Yijishan Hospital of Wannan Medical College, Wuhu, Anhui Province, China

    Xiaoming Wang

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Contributions

Yan Jin, Hao Hu, and Yitong Tian conceived and coordinated the study, drafted and revised the manuscript. Long Cheng and Xiaoyu Guo performed the cell culture and some cellular experiments. Xiaoxu Huang, Han Xu, and Qiao Yu performed the molecular experiments. Zongwei Wang, Xiaoming Wang and Gang Wang analyzed the data. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Gang Wang.

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The authors declare that they have no competing financial interests or personal relationships that may have influenced the work reported in this study.

Ethics approval and consent to participate

The present study was conducted in accordance with the relevant guidelines and regulations that govern the ethical conduct of research in this field. The human patient consent forms and protocols for this study were approved by the Wannan Medical College Ethics Committee (No: Wannan Medical College IRB2020011), and written informed consent was obtained from all participants prior to their inclusion in the study. The ethical policies and procedures for animal experiments were approved by the Animal Ethics Committee of the Academic Medical Centre at Wannan Medical College (Wuhu, China) (No: LLSC-2020-081). All animal care and experimental procedures adhered to the guidelines outlined in the Guide for the Care and Use of Laboratory Animals (2011). It is also noteworthy that no identifiable images or other personal data of participants were used in this study.

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Jin, Y., Hu, H., Tian, Y. et al. The role of LncRNA-MANCR induced by HIF-1α drive the malignant progression of pancreatic cancer by targeting miRNA-494/SIRT1 signaling axis under hypoxic conditions. Cancer Gene Ther 32, 633–648 (2025). https://doi.org/10.1038/s41417-025-00900-0

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