The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
권호 표지
DOI QR코드

DOI QR Code

Hsa_circ_0129047 sponges miR-665 to attenuate lung adenocarcinoma progression by upregulating protein tyrosine phosphatase receptor type B

  • Xiaofan Xia (Department of Respiratory and Critical Care Medicine, Wuhan Red Cross Hospital) ;
  • Jinxiu Fan (Department of Respiratory and Critical Care Medicine, Wuhan Red Cross Hospital) ;
  • Zhongjie Fan (Department of Respiratory and Critical Care Medicine, Wuhan Red Cross Hospital)
  • Received : 2022.05.10
  • Accepted : 2023.01.02
  • Published : 2023.03.01
Download PDF
⟨ Previous Next ⟩

Abstract

Compelling evidence has demonstrated the critical role of circular RNAs (circRNAs) during lung adenocarcinoma (LUAD) progression. Herein, we explored a novel circRNA, circ_0129047, and detailed its mechanism of action. The expression of circ 0129047, microRNA-665 (miR-665), and protein tyrosine phosphatase receptor type B (PTPRB) in LUAD tissues and cells was determined using reverse transcription quantitative polymerase chain reaction and Western blotting. Cell Counting Kit8 and colony formation assays were conducted to detect LUAD cell proliferation, and western blotting was performed to quantify apoptosis-related proteins (Bcl2 and Bax). Luciferase reporter and RNA immunoprecipitation assays were used to validate the predicted interaction between miR-665 and circ_0129047 or PTPRB. A xenograft assay was used for the in vivo experiments. Circ_0129047 and PTPRB were downregulated in LUAD tissues and cells, whereas miR-665 expression was upregulated. Overexpression of circ_0129047 suppresses LUAD growth in vivo and in vitro. Circ_0129047 is the target of miR-665, and the miR-665 mimic ablated the antiproliferative and pro-apoptotic phenotypes of LUAD cells by circ_0129047 augmentation. MiR-665 targets the 3'UTR of PTPRB and downregulates PTPRB expression. PTPRB overexpression offsets the pro-proliferative potential of miR-665 in LUAD cells. Circ_0129047 sequestered miR-665 and upregulated PTPRB expression, thereby reducing LUAD progression, suggesting a promising approach for preventing LUAD.

Keywords

References

  1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209-249. https://doi.org/10.3322/caac.21660
  2. Sun GZ, Zhao TW. Lung adenocarcinoma pathology stages related gene identification. Math Biosci Eng. 2019;17:737-746. https://doi.org/10.3934/mbe.2020038
  3. Kristensen LS, Andersen MS, Stagsted LVW, Ebbesen KK, Hansen TB, Kjems J. The biogenesis, biology and characterization of circular RNAs. Nat Rev Genet. 2019;20:675-691. https://doi.org/10.1038/s41576-019-0158-7
  4. Lei M, Zheng G, Ning Q, Zheng J, Dong D. Translation and functional roles of circular RNAs in human cancer. Mol Cancer. 2020;19:30.
  5. Li J, Zhang F, Li H, Peng F, Wang Z, Peng H, He J, Li Y, He L, Wei L. Circ_0010220-mediated miR-503-5p/CDCA4 axis contributes to osteosarcoma progression tumorigenesis. Gene. 2020;763:145068.
  6. Zhou J, Zhang S, Chen Z, He Z, Xu Y, Li Z. CircRNA-ENO1 promoted glycolysis and tumor progression in lung adenocarcinoma through upregulating its host gene ENO1. Cell Death Dis. 2019;10:885.
  7. Zong L, Sun Q, Zhang H, Chen Z, Deng Y, Li D, Zhang L. Increased expression of circRNA_102231 in lung cancer and its clinical significance. Biomed Pharmacother. 2018;102:639-644. https://doi.org/10.1016/j.biopha.2018.03.084
  8. Yuan DF, Wang HR, Wang ZF, Liang GH, Xing WQ, Qin JJ. CircRNA CircZMYM4 inhibits the growth and metastasis of lung adenocarcinoma via the miR-587/ODAM pathway. Biochem Biophys Res Commun. 2021;580:100-106. https://doi.org/10.1016/j.bbrc.2021.09.085
  9. Dong Y, Qiu T, Xuan Y, Liu A, Sun X, Huang Z, Su W, Du W, Yun T, Wo Y, Navarro A, Jiao W. circFBXW7 attenuates malignant progression in lung adenocarcinoma by sponging miR-942-5p. Transl Lung Cancer Res. 2021;10:1457-1473. https://doi.org/10.21037/tcr-20-2798
  10. Correia de Sousa M, Gjorgjieva M, Dolicka D, Sobolewski C, Foti M. Deciphering miRNAs' action through miRNA editing. Int J Mol Sci. 2019;20:6249.
  11. Zhang M, Wang S, Yi A, Qiao Y. microRNA-665 is down-regulated in gastric cancer and inhibits proliferation, invasion, and EMT by targeting PPP2R2A. Cell Biochem Funct. 2020;38:409-418. https://doi.org/10.1002/cbf.3485
  12. Zhao J, Yang T, Ji J, Zhao F, Li C, Han X. RHPN1-AS1 promotes cell proliferation and migration via miR-665/Akt3 in ovarian cancer. Cancer Gene Ther. 2021;28:33-41. https://doi.org/10.1038/s41417-020-0180-0
  13. Zhao XG, Hu JY, Tang J, Yi W, Zhang MY, Deng R, Mai SJ, Weng NQ, Wang RQ, Liu J, Zhang HZ, He JH, Wang HY. miR-665 expression predicts poor survival and promotes tumor metastasis by targeting NR4A3 in breast cancer. Cell Death Dis. 2019;10:479.
  14. Wang W, Ying Y, Xie H, Li J, Ma X, He L, Xu M, Chen S, Shen H, Zheng X, Liu B, Wang X, Xie L. miR-665 inhibits epithelial-tomesenchymal transition in bladder cancer via the SMAD3/SNAIL axis. Cell Cycle. 2021;20:1242-1252. https://doi.org/10.1080/15384101.2021.1929677
  15. Chen J, Li X, Yang L, Li M, Zhang Y, Zhang J. CircASH2L promotes ovarian cancer tumorigenesis, angiogenesis, and lymphangiogenesis by regulating the miR-665/VEGFA axis as a competing endogenous RNA. Front Cell Dev Biol. 2020;8:595585.
  16. Zhou P, Xiong T, Yao L, Yuan J. MicroRNA-665 promotes the proliferation of ovarian cancer cells by targeting SRCIN1. Exp Ther Med. 2020;19:1112-1120.
  17. Ying X, Zhu J, Zhang Y. Circular RNA circ-TSPAN4 promotes lung adenocarcinoma metastasis by upregulating ZEB1 via sponging miR-665. Mol Genet Genomic Med. 2019;7:e991.
  18. Huang C, Yue W, Li L, Li S, Gao C, Si L, Qi L, Cheng C, Lu M, Chen G, Cui J, Zhao R, Li Y, Tian H. Circular RNA hsa-circ-000881 suppresses the progression of lung adenocarcinoma in vitro via a miR665/PRICKLE2 axis. Ann Transl Med. 2021;9:498.
  19. Soady KJ, Tornillo G, Kendrick H, Meniel V, Olijnyk-Dallis D, Morris JS, Stein T, Gusterson BA, Isacke CM, Smalley MJ. The receptor protein tyrosine phosphatase PTPRB negatively regulates FGF2- dependent branching morphogenesis. Development. 2017;144:3777-3788. https://doi.org/10.1242/dev.149120
  20. Qi Y, Dai Y, Gui S. Protein tyrosine phosphatase PTPRB regulates Src phosphorylation and tumour progression in NSCLC. Clin Exp Pharmacol Physiol. 2016;43:1004-1012. Erratum in: Clin Exp Pharmacol Physiol. 2019;46:194.
  21. Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative CT method. Nat Protoc. 2008;3:1101-1108. https://doi.org/10.1038/nprot.2008.73
  22. Li J, Sun D, Pu W, Wang J, Peng Y. Circular RNAs in cancer: biogenesis, function, and clinical significance. Trends Cancer. 2020;6:319-336. https://doi.org/10.1016/j.trecan.2020.01.012
  23. Wang C, Tan S, Liu WR, Lei Q, Qiao W, Wu Y, Liu X, Cheng W, Wei YQ, Peng Y, Li W. RNA-Seq profiling of circular RNA in human lung adenocarcinoma and squamous cell carcinoma. Mol Cancer. 2019;18:134.
  24. Verduci L, Strano S, Yarden Y, Blandino G. The circRNA-microRNA code: emerging implications for cancer diagnosis and treatment. Mol Oncol. 2019;13:669-680. https://doi.org/10.1002/1878-0261.12468
  25. Huang ZY, Liao PJ, Liu YX, Zhong M, Sun AH, Jiang XC, Wang XP, Zhang M. Protein tyrosine phosphatase, receptor type B is a potential biomarker and facilitates cervical cancer metastasis via epithelial-mesenchymal transition. Bioengineered. 2021;12:5739-5748. https://doi.org/10.1080/21655979.2021.1968250
  26. Hu Y, Yang C, Yang S, Cheng F, Rao J, Wang X. miR-665 promotes hepatocellular carcinoma cell migration, invasion, and proliferation by decreasing Hippo signaling through targeting PTPRB. Cell Death Dis. 2018;9:954.
  27. Xia J, Li D, Zhu X, Xia W, Qi Z, Li G, Xu Q. Upregulated miR-665 expression independently predicts poor prognosis of lung cancer and facilitates tumor cell proliferation, migration and invasion. Oncol Lett. 2020;19:3578-3586. https://doi.org/10.3892/ol.2020.11457
  28. Qi Y, Dai Y, Gui S. Corrigendum: Protein tyrosine phosphatase PTPRB regulates Src phosphorylation and tumour progression in NSCLC. Clin Exp Pharmacol Physiol. 2019;46:194. Erratum for: Clin Exp Pharmacol Physiol. 2016;43:1004-1012. https://doi.org/10.1111/1440-1681.12610