DOI QR코드

DOI QR Code

MicroRNA-217 Functions as a Tumour Suppressor Gene and Correlates with Cell Resistance to Cisplatin in Lung Cancer

  • Guo, Junhua (Department of Respiratory, The First Hospital Affiliated to Henan University) ;
  • Feng, Zhijun (Department of Respiratory, The First Hospital Affiliated to Henan University) ;
  • Huang, Zhi'ang (Department of Respiratory, The First Hospital Affiliated to Henan University) ;
  • Wang, Hongyan (Department of Respiratory, The First Hospital Affiliated to Henan University) ;
  • Lu, Wujie (Department of Respiratory, The First Hospital Affiliated to Henan University)
  • Received : 2014.05.12
  • Accepted : 2014.07.31
  • Published : 2014.09.30

Abstract

MiR-217 can function as an oncogene or a tumour suppressor gene depending on cell type. However, the function of miR-217 in lung cancer remains unclear to date. This study aims to evaluate the function of miR-217 in lung cancer and investigate its effect on the sensitivity of lung cancer cells to cisplatin. The expression of miR-217 was detected in 100 patients by real-time PCR. The effects of miR-217 overexpression on the proliferation, apoptosis, migration and invasion of SPC-A-1 and A549 cells were investigated. The target gene of miR-217 was predicted by Targetscan online software, screened by dual luciferase reporter gene assay and demonstrated by Western blot. Finally, the effects of miR-217 up-regulation on the sensitivity of A549 cells to cisplatin were determined. The expression of miR-217 was significantly lower in lung cancer tissues than in noncancerous tissues (p < 0.001). The overexpression of miR-217 significantly inhibited the proliferation, migration and invasion as well as promoted the apoptosis of lung cancer cells by targeting KRAS. The up-regulation of miR-217 enhanced the sensitivity of SPC-A-1 and A549 cells to cisplatin. In conclusion, miR-217 suppresses tumour development in lung cancer by targeting KRAS and enhances cell sensitivity to cisplatin. Our results encourage researchers to use cisplatin in combination with miR-217 to treat lung cancer. This regime might lead to low-dose cisplatin application and cisplatin side-effect reduction.

Keywords

References

  1. Ambs, S., Prueitt, R.L., Yi, M., Hudson, R.S., Howe, T.M., Petrocca, F., Wallace, T.A., Liu, C.G., Volinia, S., Calin, G.A., et al. (2008). Genomic profiling of microRNA and messenger RNA reveals deregulated microRNA expression in prostate cancer. Cancer Res. 68, 6162-6170. https://doi.org/10.1158/0008-5472.CAN-08-0144
  2. Bian, H.B., Pan, X., Yang, J.S., Wang, Z.X., and De, W. (2011). Upregulation of microRNA-451 increases cisplatin sensitivity of non-small cell lung cancer cell line (A549). J. Exp. Clin. Cancer Res. 30, 20. https://doi.org/10.1186/1756-9966-30-20
  3. Cimmino, A., Calin, G.A., Fabbri, M., Iorio, M.V., Ferracin, M., Shimizu, M., Wojcik, S.E., Aqeilan, R.I., Zupo, S., Dono, M., et al. (2005). miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc. Natl. Acad. Sci. USA 102, 13944-13949. https://doi.org/10.1073/pnas.0506654102
  4. Deng, S., Calin, G.A., Croce, C.M., Coukos, G., and Zhang, L. (2008). Mechanisms of microRNA deregulation in human cancer. Cell Cycle 7, 2643-2646. https://doi.org/10.4161/cc.7.17.6597
  5. Engels, B.M., and Hutvagner, G. (2006). Principles and effects of microRNA-mediated post-transcriptional gene regulation. Oncogene 25, 6163-6169. https://doi.org/10.1038/sj.onc.1209909
  6. Esteller, M. (2011). Non-coding RNAs in human disease. Nat. Rev. Genet. 12, 861-874. https://doi.org/10.1038/nrg3074
  7. Garzon, R., Calin, G.A., and Croce, C.M. (2009). MicroRNAs in cancer. Annu. Rev. Med. 60, 167-179. https://doi.org/10.1146/annurev.med.59.053006.104707
  8. Giovannetti, E., Funel, N., Peters, G.J., Del Chiaro, M., Erozenci, L.A., Vasile, E., Leon, L.G., Pollina, L.E., Groen, A., Falcone, A., et al. (2010). MicroRNA-21 in pancreatic cancer: correlation with clinical outcome and pharmacologic aspects underlying its role in the modulation of gemcitabine activity. Cancer Res. 70, 4528-4538. https://doi.org/10.1158/0008-5472.CAN-09-4467
  9. Guttilla, I.K., and White, B.A. (2009). Coordinate regulation of FOXO1 by miR-27a, miR-96, and miR-182 in breast cancer cells. J. Biol. Chem. 284, 23204-23216. https://doi.org/10.1074/jbc.M109.031427
  10. Inomata, M., Tagawa, H., Guo, Y.M., Kameoka, Y., Takahashi, N., and Sawada, K. (2009). MicroRNA-17-92 down-regulates expression of distinct targets in different B-cell lymphoma subtypes. Blood 113, 396-402.
  11. Iorio, M.V., Visone, R., Di Leva, G., Donati, V., Petrocca, F., Casalini, P., Taccioli, C., Volinia, S., Liu, C.G., Alder, H., et al. (2007). MicroRNA signatures in human ovarian cancer. Cancer Res. 67, 8699-8707. https://doi.org/10.1158/0008-5472.CAN-07-1936
  12. Jemal, A., Siegel, R., Xu, J., and Ward, E. (2010). Cancer statistics, 2010. CA Cancer J. Clin. 60, 277-300. https://doi.org/10.3322/caac.20073
  13. Johnson, S.M., Grosshans, H., Shingara, J., Byrom, M., Jarvis, R., Cheng, A., Labourier, E., Reinert, K.L., Brown, D., and Slack, F.J. (2005). RAS is regulated by the let-7 microRNA family. Cell 120, 635-647. https://doi.org/10.1016/j.cell.2005.01.014
  14. Kato, M., Putta, S., Wang, M., Yuan, H., Lanting, L., Nair, I., Gunn, A., Nakagawa, Y., Shimano, H., Todorov, I., et al. (2009). TGF-beta activates Akt kinase through a microRNA-dependent amplifying circuit targeting PTEN. Nat. Cell Biol. 11, 881-889. https://doi.org/10.1038/ncb1897
  15. Ma, J., Dong, C., and Ji, C. (2010). MicroRNA and drug resistance. Cancer Gene Ther. 17, 523-531. https://doi.org/10.1038/cgt.2010.18
  16. Menghini, R., Casagrande, V., Cardellini, M., Martelli, E., Terrinoni, A., Amati, F., Vasa-Nicotera, M., Ippoliti, A., Novelli, G., Melino, G., et al. (2009). MicroRNA 217 modulates endothelial cell senescence via silent information regulator 1. Circulation 120, 1524-1532. https://doi.org/10.1161/CIRCULATIONAHA.109.864629
  17. Pasquinelli, A.E. (2012). MicroRNAs and their targets: recognition, regulation and an emerging reciprocal relationship. Nat. Rev. Genet. 13, 271-282.
  18. Qi, L., Bart, J., Tan, L.P., Platteel, I., Sluis, T., Huitema, S., Harms, G., Fu, L., Hollema, H., and Berg, A. (2009). Expression of miR-21 and its targets (PTEN, PDCD4, TM1) in flat epithelial atypia of the breast in relation to ductal carcinoma in situ and invasive carcinoma. BMC Cancer 9, 163. https://doi.org/10.1186/1471-2407-9-163
  19. Schepeler, T., Reinert, J.T., Ostenfeld, M.S., Christensen, L.L., Silahtaroglu, A.N., Dyrskjot, L., Wiuf, C., Sorensen, F.J., Kruhoffer, M., Laurberg, S., et al. (2008). Diagnostic and prognostic microRNAs in stage II colon cancer. Cancer Res. 68, 6416-6424. https://doi.org/10.1158/0008-5472.CAN-07-6110
  20. Slack, F.J., and Weidhaas, J.B. (2008). MicroRNA in cancer prognosis. N Engl. J. Med. 359, 2720-2722. https://doi.org/10.1056/NEJMe0808667
  21. Sorrentino, A., Liu, C.G., Addario, A., Peschle, C., Scambia, G., and Ferlini, C. (2008). Role of microRNAs in drug-resistant ovarian cancer cells. Gynecol. Oncol. 111, 478-486. https://doi.org/10.1016/j.ygyno.2008.08.017
  22. Su, J., Wang, Q., Liu, Y., and Zhong, M. (2014). miR-217 inhibits invasion of hepatocellular carcinoma cells through direct suppression of E2F3. Mol. Cell. Biochem. 392, 289-296. https://doi.org/10.1007/s11010-014-2039-x
  23. Tomari, Y., and Zamore, P.D. (2005). Perspective: machines for RNAi. Genes Dev. 19, 517-529. https://doi.org/10.1101/gad.1284105
  24. Wang, R., Wang, Z.X., Yang, J.S., Pan, X., De, W., and Chen, L.B. (2011). MicroRNA-451 functions as a tumor suppressor in human non-small cell lung cancer by targeting ras-related protein 14 (RAB14). Oncogene 30, 2644-2658. https://doi.org/10.1038/onc.2010.642
  25. Yu, S., Lu, Z., Liu, C., Meng, Y., Ma, Y., Zhao, W., Liu, J., Yu, J., and Chen, J. (2010a). miRNA-96 suppresses KRAS and functions as a tumor suppressor gene in pancreatic cancer. Cancer Res. 70, 6015-6025. https://doi.org/10.1158/0008-5472.CAN-09-4531
  26. Yu, Z.W., Zhong, L.P., Ji, T., Zhang, P., Chen, W.T., and Zhang, C.P. (2010b). MicroRNAs contribute to the chemoresistance of cisplatin in tongue squamous cell carcinoma lines. Oral Oncol. 46, 317-322. https://doi.org/10.1016/j.oraloncology.2010.02.002
  27. Zhang, B., Pan, X., Cobb, G.P., and Anderson, T.A. (2007). microRNAs as oncogenes and tumor suppressors. Dev. Biol. 302, 1-12. https://doi.org/10.1016/j.ydbio.2006.08.028
  28. Zhang, T., Wang, Q., Zhao, D., Cui, Y., Cao, B., Guo, L., and Lu, S.H. (2011). The oncogenetic role of microRNA-31 as a potential biomarker in oesophageal squamous cell carcinoma. Clin. Sci. 121, 437-447. https://doi.org/10.1042/CS20110207
  29. Zhang, H.S., Wu, T.C., Sang, W.W., and Ruan, Z. (2012). MiR-217 is involved in Tat-induced HIV-1 long terminal repeat (LTR) transactivation by down-regulation of SIRT1. Biochim. Biophys. Acta 1823, 1017-1023. https://doi.org/10.1016/j.bbamcr.2012.02.014
  30. Zhao, W.G., Yu, S.N., Lu, Z.H., Ma, Y.H., Gu, Y.M., and Chen, J. (2010). The miR-217 microRNA functions as a potential tumor suppressor in pancreatic ductal adenocarcinoma by targeting KRAS. Carcinogenesis 31, 1726-1733. https://doi.org/10.1093/carcin/bgq160

Cited by

  1. Regulation of Complement-Dependent Cytotoxicity by MicroRNAs miR-200b, miR-200c, and miR-217 vol.196, pp.12, 2016, https://doi.org/10.4049/jimmunol.1502701
  2. New strategies for targeting drug combinations to overcome mutation-driven drug resistance vol.42, 2017, https://doi.org/10.1016/j.semcancer.2016.11.002
  3. Quercetin Enhances Cisplatin Sensitivity of Human Osteosarcoma Cells by Modulating microRNA-217-KRAS Axis vol.38, pp.7, 2015, https://doi.org/10.14348/molcells.2015.0037
  4. miR-30a Regulates the Expression of CAGE and p53 and Regulates the Response to Anti-Cancer Drugs vol.39, pp.4, 2016, https://doi.org/10.14348/molcells.2016.2242
  5. TTBK2 circular RNA promotes glioma malignancy by regulating miR-217/HNF1β/Derlin-1 pathway vol.10, pp.1, 2017, https://doi.org/10.1186/s13045-017-0422-2
  6. Identifying the miRNA signature associated with survival time in patients with lung adenocarcinoma using miRNA expression profiles vol.7, pp.1, 2017, https://doi.org/10.1038/s41598-017-07739-y
  7. Integrated Analysis and MicroRNA Expression Profiling Identified Seven miRNAs Associated With Progression of Oral Squamous Cell Carcinoma vol.232, pp.8, 2017, https://doi.org/10.1002/jcp.25728
  8. Downregulation of ULK1 by microRNA-372 inhibits the survival of human pancreatic adenocarcinoma cells vol.108, pp.9, 2017, https://doi.org/10.1111/cas.13315
  9. Posttranscriptional silencing of the lncRNA MALAT1 by miR-217 inhibits the epithelial–mesenchymal transition via enhancer of zeste homolog 2 in the malignant transformation of HBE cells induced by cigarette smoke extract vol.289, pp.2, 2015, https://doi.org/10.1016/j.taap.2015.09.016
  10. Interactions between anticancer active platinum complexes and non-coding RNAs/microRNAs vol.2, pp.1, 2016, https://doi.org/10.1016/j.ncrna.2016.10.001
  11. miR-217 suppresses proliferation, migration, and invasion promoting apoptosis via targeting MTDH in hepatocellular carcinoma vol.37, pp.3, 2017, https://doi.org/10.3892/or.2017.5401
  12. The lncRNA MALAT1 acts as a competing endogenous RNA to regulate KRAS expression by sponging miR-217 in pancreatic ductal adenocarcinoma vol.7, pp.1, 2017, https://doi.org/10.1038/s41598-017-05274-4
  13. miR-217 regulates tumor growth and apoptosis by targeting the MAPK signaling pathway in colorectal cancer vol.12, pp.6, 2016, https://doi.org/10.3892/ol.2016.5249
  14. MicroRNA 217 inhibits cell proliferation and enhances chemosensitivity to doxorubicin in acute myeloid leukemia by targeting KRAS vol.13, pp.6, 2017, https://doi.org/10.3892/ol.2017.6076
  15. miR-98 targets ITGB3 to inhibit proliferation, migration, and invasion of non-small-cell lung cancer vol.8, pp.None, 2014, https://doi.org/10.2147/ott.s90998
  16. Activation of endoplasmic reticulum stress promotes autophagy and apoptosis and reverses chemoresistance of human small cell lung cancer cells by inhibiting the PI3K/AKT/mTOR signaling pathway vol.7, pp.47, 2014, https://doi.org/10.18632/oncotarget.12718
  17. Correlation between serum IL-1β and miR-144-3p as well as their prognostic values in LUAD and LUSC patients vol.7, pp.52, 2016, https://doi.org/10.18632/oncotarget.13042
  18. Endoplasmic reticulum stress promotes autophagy and apoptosis and reverses chemoresistance in human ovarian cancer cells vol.8, pp.30, 2017, https://doi.org/10.18632/oncotarget.17673
  19. MicroRNAs as regulators of cisplatin-resistance in non-small cell lung carcinomas vol.8, pp.70, 2014, https://doi.org/10.18632/oncotarget.22975
  20. Regulation of actin-binding protein ANLN by antitumor miR-217 inhibits cancer cell aggressiveness in pancreatic ductal adenocarcinoma vol.8, pp.32, 2014, https://doi.org/10.18632/oncotarget.18261
  21. Noncoding RNA in drug resistant sarcoma vol.8, pp.40, 2014, https://doi.org/10.18632/oncotarget.19029
  22. Polymorphisms of rs1347093 and rs1397529 are associated with lung cancer risk in northeast Chinese population vol.8, pp.55, 2017, https://doi.org/10.18632/oncotarget.22030
  23. lncRNA PCAT6 promotes non-small cell lung cancer cell proliferation, migration and invasion through regulating miR-330-5p vol.11, pp.None, 2018, https://doi.org/10.2147/ott.s178597
  24. Downregulated miR-217 expression predicts a poor outcome in acute myeloid leukemia vol.22, pp.1, 2018, https://doi.org/10.3233/cbm-170936
  25. MicroRNA-217 acts as a tumor suppressor and correlates with the chemoresistance of cervical carcinoma to cisplatin vol.12, pp.None, 2019, https://doi.org/10.2147/ott.s176618
  26. MiR-155-5p accelerates the metastasis of cervical cancer cell via targeting TP53INP1 vol.12, pp.None, 2014, https://doi.org/10.2147/ott.s193097
  27. MiR-217 Inhibits Proliferation, Migration, and Invasion by Targeting SIRT1 in Osteosarcoma vol.34, pp.4, 2014, https://doi.org/10.1089/cbr.2017.2394
  28. Expression of selected miRNA, RARβ and FHIT genes in BALf of squamous cell lung cancer (squamous-cell carcinoma, SCC) patients: a pilot study vol.46, pp.6, 2014, https://doi.org/10.1007/s11033-019-05057-2
  29. Promotion of miR-221-5p on the Sensitivity of Gastric Cancer Cells to Cisplatin and Its Effects on Cell Proliferation and Apoptosis by Regulating DDR1 vol.13, pp.None, 2014, https://doi.org/10.2147/ott.s232953
  30. Long Non-Coding RNA Myosin Light Chain Kinase Antisense 1 Plays an Oncogenic Role in Gallbladder Carcinoma by Promoting Chemoresistance and Proliferation vol.13, pp.None, 2014, https://doi.org/10.2147/cmar.s323759
  31. MicroRNA-217 modulates inflammation, oxidative stress, and lung injury in septic mice via SIRT1 vol.55, pp.1, 2021, https://doi.org/10.1080/10715762.2020.1852234
  32. Improving Gemcitabine Sensitivity in Pancreatic Cancer Cells by Restoring miRNA-217 Levels vol.11, pp.5, 2014, https://doi.org/10.3390/biom11050639
  33. Potential of natural products in osteosarcoma treatment: Focus on molecular mechanisms vol.144, pp.None, 2014, https://doi.org/10.1016/j.biopha.2021.112257