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CASC11 promotes aggressiveness of prostate cancer cells through miR-145/IGF1R axis

Subjects

Abstract

Background

Prostate cancer (PCa) is the most common malignancy diagnosed among men after lung cancer in developed countries. Investigation of the underlying molecular mechanisms of PCa is urgently needed in order to develop better therapeutic strategies and to reveal more effective therapeutic targets. In this study, we aimed at exploring the potential functions of CASC11 in association with miR-145 and IGF1R during the malignant progression of PCa cells.

Methods

We initially investigated the oncogenic potential of noncoding members of CASC gene family and analyzed the effects of CASC11 overexpression on proliferation, migration, and colony formation ability of DU145, LNCaP, and PC3 PCa cells. We, then, exprlored the association of CASC11, miR-145, and IGF1R expression and their impacts on PI3K/AKT/mTOR signaling pathway in in vitro models.

Results

In silico analysis revealed that of the CASC family only CASC11 showed consistent results considering its differential expression as well as its association with the overall survival of patients. We demonstrated that ectopic overexpression of CASC11 significantly increased the proliferation, colony formation, and migration capacity in all three cell lines. CASC11 overexpression caused suppression of miR-145 and overexpression of IGF1R, leading to activation of PI3K/AKT/mTOR signaling pathway.

Conclusion

In summary, we found that CASC11 is upregulated in PCa cells and clinical tumor samples in comparison to corresponding controls and revealed that ectopic CASC11 overexpression promotes cellular phenotypes associated with PCa progression through CASC11/miR-145/IGF1R axis.

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Fig. 1: CASC11 serves as an important candidate with oncogenic function among CASC family members.
Fig. 2: CASC11 promoted the proliferation and colony formation capacities of PCa cells.
Fig. 3: CASC11 induced the migration of PCa cells.
Fig. 4: CASC11 exerts its oncogenic functions through miR-145/IGF1R axis.
Fig. 5: CASC11 participates in prostate carcinogenesis via dysregulation of PI3K/Akt/mTOR pathway.

References

  1. 1.

    Ma Y, Fan B, Ren Z, Liu B, Wang Y. Long noncoding RNA DANCR contributes to docetaxel resistance in prostate cancer through targeting the miR-34a-5p/JAG1 pathway. Onco Targets Ther. 2019;12:5485–97.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  2. 2.

    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:7–34.

    Article  Google Scholar 

  3. 3.

    Janiczek M, Szylberg Ł, Kasperska A, Kowalewski A, Parol M, Antosik P, et al. Immunotherapy as a promising treatment for prostate cancer: a systematic review. J Immunol Res. 2017;2017:4861570.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  4. 4.

    Tian C, Deng Y, Jin Y, Shi S, Bi H. Long non-coding RNA RNCR3 promotes prostate cancer progression through targeting miR-185-5p. Am J Transl Res. 2018;10:1562–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Xu YH, Deng JL, Wang G, Zhu YS. Long non-coding RNAs in prostate cancer: Functional roles and clinical implications. Cancer Lett. 2019;464:37–55.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  6. 6.

    Maruyama R, Suzuki H. Long noncoding RNA involvement in cancer. BMB Rep. 2012;45:604–11.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  7. 7.

    Chen X, Sun Y, Cai R, Wang G, Shu X, Pang W. Long noncoding RNA: multiple players in gene expression. BMB Rep. 2018;51:280–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  8. 8.

    Yu H, Zhou W, Yan W, Xu Z, Xie Y, Zhang P. LncRNA CASC11 is upregulated in postmenopausal osteoporosis and is correlated with TNF-α. Clin Inter Aging. 2019;14:1663–9.

    CAS  Article  Google Scholar 

  9. 9.

    Hsu W, Liu L, Chen X, Zhang Y, Zhu W. LncRNA CASC11 promotes the cervical cancer progression by activating Wnt/beta-catenin signaling pathway. Biol Res. 2019;52:33.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  10. 10.

    Denaro N, Merlano MC, Lo Nigro C. Long noncoding RNAs as regulators of cancer immunity. Mol Oncol. 2019;13:61–73.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  11. 11.

    Misawa A, Takayama KI, Inoue S. Long non-coding RNAs and prostate cancer. Cancer Sci. 2017;108:2107–14.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  12. 12.

    Zhang Z, Zhou C, Chang Y, Hu Y, Zhang F, Lu Y, et al. Long non-coding RNA CASC11 interacts with hnRNP-K and activates the WNT/β-catenin pathway to promote growth and metastasis in colorectal cancer. Cancer Lett. 2016;376:62–73.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  13. 13.

    Han Y, Chen M, Wang A, Fan X. STAT3-induced upregulation of lncRNA CASC11 promotes the cell migration, invasion and epithelial-mesenchymal transition in hepatocellular carcinoma by epigenetically silencing PTEN and activating PI3K/AKT signaling pathway. Biochem Biophys Res Commun. 2019;508:472–9.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  14. 14.

    Zhang L, Kang W, Lu X, Ma S, Dong L, Zou B. LncRNA CASC11 promoted gastric cancer cell proliferation, migration and invasion in vitro by regulating cell cycle pathway. Cell Cycle. 2018;17:1886–1900.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  15. 15.

    Lin HY, Callan CY, Fang Z, Tung HY, Park JY. Interactions of. Cancer Epidemiol Biomark Prev. 2019;28:1067–75.

    CAS  Article  Google Scholar 

  16. 16.

    Kilic A, Barlak N, Sanli F, Aytatli A, Capik O, Karatas OF. Mode of action of carboplatin via activating p53/miR-145 axis in head and neck cancers. Laryngoscope. 2019;130:2818–24.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  17. 17.

    Ghorbanmehr N, Gharbi S, Korsching E, Tavallaei M, Einollahi B, Mowla SJ. miR-21-5p, miR-141-3p, and miR-205-5p levels in urine-promising biomarkers for the identification of prostate and bladder cancer. Prostate. 2019;79:88–95.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  18. 18.

    Hasegawa T, Glavich GJ, Pahuski M, Short A, Semmes OJ, Yang L, et al. Characterization and evidence of the miR-888 cluster as a novel cancer network in prostate. Mol Cancer Res. 2018;16:669–81.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  19. 19.

    Tinay I, Tan M, Gui B, Werner L, Kibel AS, Jia L. Functional roles and potential clinical application of miRNA-345-5p in prostate cancer. Prostate. 2018;78:927–37.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  20. 20.

    Wang L, Tang H, Thayanithy V, Subramanian S, Oberg AL, Cunningham JM, et al. Gene networks and microRNAs implicated in aggressive prostate cancer. Cancer Res. 2009;69:9490–7.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  21. 21.

    Ekin A, Karatas OF, Culha M, Ozen M. Designing a gold nanoparticle-based nanocarrier for microRNA transfection into the prostate and breast cancer cells. J Gene Med. 2014;16:331–5.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  22. 22.

    Karatas OF, Yuceturk B, Suer I, Yilmaz M, Cansiz H, Solak M, et al. Role of miR-145 in human laryngeal squamous cell carcinoma. Head Neck. 2016;38:260–6.

    PubMed  Article  PubMed Central  Google Scholar 

  23. 23.

    Seven M, Karatas OF, Duz MB, Ozen M. The role of miRNAs in cancer: from pathogenesis to therapeutic implications. Future Oncol. 2014;10:1027–48.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  24. 24.

    Tang Z, Kang B, Li C, Chen T, Zhang Z. GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res. 2019;47:W556–60.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  25. 25.

    Chandrashekar DS, Bashel B, Balasubramanya SAH, Creighton CJ, Ponce-Rodriguez I, Chakravarthi BVSK, et al. UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia. 2017;19:649–58.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  26. 26.

    Ghandi M, Huang FW, Jané-Valbuena J, Kryukov GV, Lo CC, McDonald ER, et al. Next-generation characterization of the cancer cell line encyclopedia. Nature. 2019;569:503–8.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  27. 27.

    Mann M, Wright PR, Backofen R. IntaRNA 2.0: enhanced and customizable prediction of RNA-RNA interactions. Nucleic Acids Res. 2017;45:W435–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  28. 28.

    Ye Y, Yuan XH, Wang JJ, Wang YC, Li SL. The diagnostic value of miRNA-141 in prostate cancer: a systematic review and PRISMA-compliant meta-analysis. Medicine (Baltimore). 2020;99:e19993.

    Article  Google Scholar 

  29. 29.

    Örs Kumoğlu G, Döşkaya M, Gulce Iz S. The biomarker features of miR-145-3p determined via meta-analysis validated by qRT-PCR in metastatic cancer cell lines. Gene. 2019;710:341–53.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  30. 30.

    Zhou H, Zhu X. MicroRNA-21 and microRNA-30c as diagnostic biomarkers for prostate cancer: a meta-analysis. Cancer Manag Res. 2019;11:2039–50.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  31. 31.

    He S, Shi J, Mao J, Luo X, Liu W, Liu R, et al. The expression of miR-375 in prostate cancer: A study based on GEO, TCGA data and bioinformatics analysis. Pathol Res Pr. 2019;215:152375.

    CAS  Article  Google Scholar 

  32. 32.

    Xie ZC, Huang JC, Zhang LJ, Gan BL, Wen DY, Chen G, et al. Exploration of the diagnostic value and molecular mechanism of miR‑1 in prostate cancer: a study based on meta‑analyses and bioinformatics. Mol Med Rep. 2018;18:5630–46.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Yan HB, Zhang Y, Cen JM, Wang X, Gan BL, Huang JC, et al. Expression of microRNA-99a-3p in prostate cancer based on bioinformatics data and meta-analysis of a literature review of 965 cases. Med Sci Monit. 2018;24:4807–22.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  34. 34.

    Li D, Hao X, Song Y. Identification of the key MicroRNAs and the miRNA-mRNA regulatory pathways in prostate cancer by bioinformatics methods. Biomed Res Int. 2018;2018:6204128.

    PubMed  PubMed Central  Google Scholar 

  35. 35.

    Khorasani M, Shahbazi S, Hosseinkhan N, Mahdian R. Analysis of differential expression of microRNAs and their target genes in prostate cancer: a bioinformatics study on microarray gene expression data. Int J Mol Cell Med. 2019;8:103–14.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Paller CJ, Antonarakis ES. Management of biochemically recurrent prostate cancer after local therapy: evolving standards of care and new directions. Clin Adv Hematol Oncol. 2013;11:14–23.

    PubMed  PubMed Central  Google Scholar 

  37. 37.

    Hua JT, Chen S, He HH. Landscape of noncoding RNA in prostate cancer. Trends Genet. 2019;35:840–51.

    CAS  PubMed  Article  Google Scholar 

  38. 38.

    Iyer MK, Niknafs YS, Malik R, Singhal U, Sahu A, Hosono Y, et al. The landscape of long noncoding RNAs in the human transcriptome. Nat Genet. 2015;47:199–208.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  39. 39.

    Cui Y, Shen G, Zhou D, Wu F. CASC11 overexpression predicts poor prognosis and regulates cell proliferation and apoptosis in ovarian carcinoma. Cancer Manag Res. 2020;12:523–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  40. 40.

    Yan R, Jiang Y, Lai B, Lin Y, Wen J. The positive feedback loop FOXO3/CASC11/miR-498 promotes the tumorigenesis of non-small cell lung cancer. Biochem Biophys Res Commun. 2019;519:518–24.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  41. 41.

    Luo H, Xu C, Le W, Ge B, Wang T. lncRNA CASC11 promotes cancer cell proliferation in bladder cancer through miRNA-150. J Cell Biochem. 2019;120:13487–93.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  42. 42.

    Chen J, Dang J. LncRNA CASC11 was downregulated in coronary artery disease and inhibits transforming growth factor. J Int Med Res. 2020;48:300060519889187.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Liang F, Yue J, Wang J, Zhang L, Fan R, Zhang H, et al. GPCR48/LGR4 promotes tumorigenesis of prostate cancer via PI3K/Akt signaling pathway. Med Oncol. 2015;32:49.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  44. 44.

    Wang H, Fang R, Wang XF, Zhang F, Chen DY, Zhou B, et al. Stabilization of Snail through AKT/GSK-3β signaling pathway is required for TNF-α-induced epithelial-mesenchymal transition in prostate cancer PC3 cells. Eur J Pharm. 2013;714:48–55.

    CAS  Article  Google Scholar 

  45. 45.

    Chen X, Yu Q, Pan H, Li P, Wang X, Fu S. Overexpression of IGFBP5 enhances radiosensitivity through PI3K-AKT pathway in prostate cancer. Cancer Manag Res. 2020;12:5409–18.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  46. 46.

    Wei A, Fan B, Zhao Y, Zhang H, Wang L, Yu X, et al. ST6Gal-I overexpression facilitates prostate cancer progression via the PI3K/Akt/GSK-3β/β-catenin signaling pathway. Oncotarget. 2016;7:65374–88.

    PubMed  PubMed Central  Article  Google Scholar 

  47. 47.

    Liao X, Thrasher JB, Holzbeierlein J, Stanley S, Li B. Glycogen synthase kinase-3beta activity is required for androgen-stimulated gene expression in prostate cancer. Endocrinology. 2004;145:2941–9.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  48. 48.

    Shorning BY, Dass MS, Smalley MJ, Pearson HB. The PI3K-AKT-mTOR pathway and prostate cancer: at the crossroads of AR, MAPK, and WNT signaling. Int J Mol Sci. 2020;21:4507.

    CAS  PubMed Central  Article  Google Scholar 

  49. 49.

    Toren P, Zoubeidi A. Targeting the PI3K/Akt pathway in prostate cancer: challenges and opportunities (review). Int J Oncol. 2014;45:1793–801.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  50. 50.

    Heidegger I, Kern J, Ofer P, Klocker H, Massoner P. Oncogenic functions of IGF1R and INSR in prostate cancer include enhanced tumor growth, cell migration and angiogenesis. Oncotarget. 2014;5:2723–35.

    PubMed  PubMed Central  Article  Google Scholar 

  51. 51.

    Su J, Liang H, Yao W, Wang N, Zhang S, Yan X, et al. MiR-143 and MiR-145 regulate IGF1R to suppress cell proliferation in colorectal cancer. PLoS ONE. 2014;9:e114420.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  52. 52.

    Frasca F, Pandini G, Sciacca L, Pezzino V, Squatrito S, Belfiore A, et al. The role of insulin receptors and IGF-I receptors in cancer and other diseases. Arch Physiol Biochem. 2008;114:23–37.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  53. 53.

    Vanamala J, Reddivari L, Radhakrishnan S, Tarver C. Resveratrol suppresses IGF-1 induced human colon cancer cell proliferation and elevates apoptosis via suppression of IGF-1R/Wnt and activation of p53 signaling pathways. BMC Cancer. 2010;10:238.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  54. 54.

    Zhu Z, Xu T, Wang L, Wang X, Zhong S, Xu C, et al. MicroRNA-145 directly targets the insulin-like growth factor receptor I in human bladder cancer cells. FEBS Lett. 2014;588:3180–5.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

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Correspondence to Omer Faruk Karatas.

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OC, FS, AK, OC, IS, MK, and MI declare that they have no conflict of interests. OFK holds stocks in EcoTech Biotechnology. The terms of this arrangement have been reviewed and approved by Erzurum Technical University in accordance with its policy on objectivity in research.

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Capik, O., Sanli, F., Kurt, A. et al. CASC11 promotes aggressiveness of prostate cancer cells through miR-145/IGF1R axis. Prostate Cancer Prostatic Dis (2021). https://doi.org/10.1038/s41391-021-00353-0

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