Molecules and Cells

  • 제41권6호
  • /
  • Pages.532-544
  • /
  • 2018
  • /
  • 1016-8478(pISSN)
  • /
  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
권호 표지
DOI QR코드

DOI QR Code

MiR-374b Promotes Proliferation and Inhibits Apoptosis of Human GIST Cells by Inhibiting PTEN through Activation of the PI3K/Akt Pathway

  • Long, Zi-Wen (Department of Surgery, Shigatse People's Hospital) ;
  • Wu, Jiang-Hong (Department of Gastric Cancer Surgery, Fudan University Shanghai Cancer Center) ;
  • Hong, Cai (Department of Gastric Cancer Surgery, Fudan University Shanghai Cancer Center) ;
  • Wang, Ya-Nong (Department of Gastric Cancer Surgery, Fudan University Shanghai Cancer Center) ;
  • Zhou, Ye (Department of Gastric Cancer Surgery, Fudan University Shanghai Cancer Center)
  • 투고 : 2017.09.11
  • 심사 : 2018.03.21
  • 발행 : 2018.06.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. In order to investigate a new treatment fot GIST, we hypothesized the effect of miR-374b targeting PTEN gene-mediated PI3K/Akt signal transduction pathway on proliferation and apoptosis of human gastrointestinal stromal tumor (GIST) cells. We obtained GIST tissues and adjacent normal tissues from 143 patients with GIST to measure the levels of miR-374b, PTEN, PI3K, Akt, caspase9, Bax, MMP2, MMP9, ki67, PCNA, P53 and cyclinD1. Finally, cell viability, cell cycle and apoptosis were detected. According to the KFGG analysis of DEGs, PTEN was involved in a variety of signaling pathways and miRs were associated with cancer development. The results showed that MiR-374b was highly expressed, while PTEN was downregulated in the GIST tissues. The levels of miR-374b, PI3K, AKT and PTEN were related to tumor diameter and pathological stage. Additionally, miR-374b increased the mRNA and protein levels of PI3K, Akt, MMP2, MMP9, P53 and cyclinD1, suggesting that miR-374b activates PI3K/Akt signaling pathway in GIST-T1 cells. Moreover, MiR374b promoted cell viability, migration, invasion, and cell cycle entry, and inhibited apoptosis in GIST cells. Taken together, the results indicated that miR-374b promotes viability and inhibits apoptosis of human GIST cells by targeting PTEN gene through the PI3K/Akt signaling pathway. Thus, this study provides a new potential target for GIST treatment.

키워드

참고문헌

  1. Cao, C.L., Niu, H.J., Kang, S.P., Cong, C.L., and Kang, S.R. (2016). miRNA-21 sensitizes gastrointestinal stromal tumors (GISTs) cells to Imatinib via targeting B-cell lymphoma 2 (Bcl-2). Eur. Rev. Med. Pharmacol. Sci. 20, 3574-3581.
  2. Chen, L., Wang, J., Wang, B., Yang, J., Gong, Z., Zhao, X., Zhang, C., and Du, K. (2016). MiR-126 inhibits vascular endothelial cell apoptosis through targeting PI3K/Akt signaling. Ann. Hematol. 95, 365-374. https://doi.org/10.1007/s00277-015-2567-9
  3. Choi, H.J., Lee, H., Kim, H., Kwon, J.E., Kang, H.J., You, K.T., Rhee, H., Noh, S.H., Paik, Y.K., Hyung, W. J., Kim, H. (2010). MicroRNA expression profile of gastrointestinal stromal tumors is distinguished by 14q loss and anatomic site. Int. J. Cancer 126, 1640-1650.
  4. Dong, P., Konno, Y., Watari, H., Hosaka, M., Noguchi, M., and Sakuragi, N. (2014). The impact of microRNA-mediated PI3K/AKT signaling on epithelial-mesenchymal transition and cancer stemness in endometrial cancer. J. Transl. Med. 12, 231. https://doi.org/10.1186/s12967-014-0231-0
  5. Fresno Vara, J.A., Casado, E., de Castro, J., Cejas, P., Belda-Iniesta, C., and Gonzalez-Baron, M. (2004). PI3K/Akt signalling pathway and cancer. Cancer Treat. Rev. 30, 193-204. https://doi.org/10.1016/j.ctrv.2003.07.007
  6. Fujita, A., Sato, J.R., Rodrigues Lde, O., Ferreira, C.E., and Sogayar, M. C. (2006). Evaluating different methods of microarray data normalization. BMC bioinformatics 7, 469. https://doi.org/10.1186/1471-2105-7-469
  7. Gao, Q., Ye, F., Xia, X., Xing, H., Lu, Y., Zhou, J., and Ma, D. (2009). Correlation between PTEN expression and PI3K/Akt signal pathway in endometrial carcinoma. J. Huazhong Univ. Sci. Technolog. Med. Sci. 29, 59-63. https://doi.org/10.1007/s11596-009-0112-6
  8. Hu, S., Bao, H., Xu, X., Zhou, X., Qin, W., Zeng, C., and Liu, Z. (2015). Increased miR-374b promotes cell proliferation and the production of aberrant glycosylated IgA1 in B cells of IgA nephropathy. FEBS Lett. 589, 4019-4025. https://doi.org/10.1016/j.febslet.2015.10.033
  9. Isosaka, M., Niinuma, T., Nojima, M., Kai, M., Yamamoto, E., Maruyama, R., Nobuoka, T., Nishida, T., Kanda, T., Taguchi, T., et al. (2015). A screen for epigenetically silenced microRNA genes in gastrointestinal stromal tumors. PloS one 10, e0133754. https://doi.org/10.1371/journal.pone.0133754
  10. Kanehisa, M., and Goto, S. (2000). KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28, 27-30. https://doi.org/10.1093/nar/28.1.27
  11. Lanke, G., and Lee, J.H. (2017). How best to manage gastrointestinal stromal tumor. World J. Clin. Oncol. 8, 135-144. https://doi.org/10.5306/wjco.v8.i2.135
  12. Li, P., Mao, W.M., Zheng, Z.G., Dong, Z.M., and Ling, Z.Q. (2013). Down-regulation of PTEN expression modulated by dysregulated miR-21 contributes to the progression of esophageal cancer. Dig. Dis. Sci. 58, 3483-3493. https://doi.org/10.1007/s10620-013-2854-z
  13. Liu, G.L., Yang, H.J., Liu, B., and Liu, T. (2017). Effects of microRNA-19b on the proliferation, apoptosis, and migration of Wilms' Tumor cells via the PTEN/PI3K/AKT signaling pathway. J. Cell. Biochem. 118, 3424-3434. https://doi.org/10.1002/jcb.25999
  14. Lu, X.X., Cao, L.Y., Chen, X., Xiao, J., Zou, Y., and Chen, Q. (2016). PTEN inhibits cell proliferation, promotes cell apoptosis, and induces cell cycle arrest via downregulating the PI3K/AKT/hTERT pathway in lung adenocarcinoma A549 cells. BioMed Res. Int. 2016, 2476842.
  15. Maehama, T. (2007). PTEN: its deregulation and tumorigenesis. Biol. Pharmaceut. Bull. 30, 1624-1627. https://doi.org/10.1248/bpb.30.1624
  16. Markou, A., Zavridou, M., and Lianidou, E.S. (2016). miRNA-21 as a novel therapeutic target in lung cancer. Lung Cancer (Auckl) 7, 19-27.
  17. Miettinen, M., and Lasota, J. (2001). Gastrointestinal stromal tumors--definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Archiv. 438, 1-12. https://doi.org/10.1007/s004280000338
  18. Mogensen, C.E., and Hansen, K.W. (1990). Preventing or postponing renal disease in insulin-dependent diabetes by glycemic and nonglycemic intervention. Contrib. Nephrol. 78, 73-100; discussion 100-101.
  19. Sato, T., Shiba-Ishii, A., Kim, Y., Dai, T., Husni, R.E., Hong, J., Kano, J., Sakashita, S., Iijima, T., and Noguchi, M. (2017). miR-3941: A novel microRNA that controls IGBP1 expression and is associated with malignant progression of lung adenocarcinoma. Cancer Sci. 108, 536-542. https://doi.org/10.1111/cas.13148
  20. Smyth, G.K. (2004). Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat. Appl. Genet. Mol. Biol. 3, Article3.
  21. Tao, K., Yang, J., Guo, Z., Hu, Y., Sheng, H., Gao, H., and Yu, H. (2014). Prognostic value of miR-221-3p, miR-342-3p and miR-491-5p expression in colon cancer. Am. J. Transl. Res. 6, 391-401.
  22. Tsang, V.H., Dwight, T., Benn, D.E., Meyer-Rochow, G.Y., Gill, A.J., Sywak, M., Sidhu, S., Veivers, D., Sue, C.M., et al. (2014). Overexpression of miR-210 is associated with SDH-related pheochromocytomas, paragangliomas, and gastrointestinal stromal tumours. Endoc. Relat. Cancer 21, 415-426. https://doi.org/10.1530/ERC-13-0519
  23. Tu, K., Liu, Z., Yao, B., Han S., and Yang W. (2016). MicroRNA-519a promotes tumor growth by targeting PTEN/PI3K/AKT signaling in hepatocellular carcinoma. Int. J. Oncol. 48, 965-974. https://doi.org/10.3892/ijo.2015.3309
  24. Valsangkar, N., Sehdev, A., Misra, S., Zimmers, T.A., O'Neil, B.H., and Koniaris, L.G. (2015). Current management of gastrointestinal stromal tumors: Surgery, current biomarkers, mutations, and therapy. Surgery 158, 1149-1164. https://doi.org/10.1016/j.surg.2015.06.027
  25. Wang, P., Zou, F., Zhang, X., Li, H., Dulak, A., Tomko, R. J., Jr., Lazo, J.S., Wang, Z., Zhang, L., and Yu, J. (2009). microRNA-21 negatively regulates Cdc25A and cell cycle progression in colon cancer cells. Cancer Res. 69, 8157-8165. https://doi.org/10.1158/0008-5472.CAN-09-1996
  26. Wu, W. K., Lee C. W., Cho, C.H., Fan, D., Wu, K., Yu, J., and Sung, J.J. (2010). MicroRNA dysregulation in gastric cancer: a new player enters the game. Oncogene 29, 5761-5771. https://doi.org/10.1038/onc.2010.352
  27. Wu, X., Li, S., Xu, X., Wu, S., Chen, R., Jiang, Q., Li, Y., and Xu, Y. (2015). The potential value of miR-1 and miR-374b as biomarkers for colorectal cancer. Int J. Clin. Exp. Pathol. 8, 2840-2851.
  28. Wu, Y.R., Qi, H.J., Deng, D.F., Luo, Y.Y., and Yang, S.L. (2016). MicroRNA-21 promotes cell proliferation, migration, and resistance to apoptosis through PTEN/PI3K/AKT signaling pathway in esophageal cancer. Tumour Biol. 37, 12061-12070. https://doi.org/10.1007/s13277-016-5074-2
  29. Xiong, J., Li, Z., Zhang, Y., Li, D., Zhang, G., Luo, X., Jie, Z., Liu, Y., Cao, Y., Le, Z., et al. (2016). PRL-3 promotes the peritoneal metastasis of gastric cancer through the PI3K/Akt signaling pathway by regulating PTEN. Oncol. Rep. 36, 1819-1828. https://doi.org/10.3892/or.2016.5030
  30. Yang, Z., Fang, S., Di, Y., Ying, W., Tan, Y., and Gu, W. (2015). Modulation of NF-kappaB/miR-21/PTEN pathway sensitizes non-small cell lung cancer to cisplatin. PloS one 10, e0121547. https://doi.org/10.1371/journal.pone.0121547
  31. Ye, M., Li, J., and Gong, J. (2017). PCDH10 gene inhibits cell proliferation and induces cell apoptosis by inhibiting the PI3K/Akt signaling pathway in hepatocellular carcinoma cells. Oncology Rep. 37, 3167-3174. https://doi.org/10.3892/or.2017.5630
  32. Ying, J., Xu, Q., Liu, B., Zhang, G., Chen, L., and Pan, H. (2015). The expression of the PI3K/AKT/mTOR pathway in gastric cancer and its role in gastric cancer prognosis. Onco Targets Ther. 8, 2427-2433.
  33. Yu, G., Wang, L.G., Han, Y., and He, Q.Y. (2012). clusterProfiler: an R package for comparing biological themes among gene clusters. Omics 16, 284-287. https://doi.org/10.1089/omi.2011.0118
  34. Zhang, Z., Li, Z., Ga,o C., Chen, P., Chen, J., Liu, W., Xiao, S., and Lu, H. (2008). miR-21 plays a pivotal role in gastric cancer pathogenesis and progression. Lab. Invest. 88, 1358-1366. https://doi.org/10.1038/labinvest.2008.94
  35. Zhu, C.Z., Liu, D., Kang, W.M., Yu, J.C., Ma Z.Q., Ye, X., and Li, K. (2017). Ghrelin and gastrointestinal stromal tumors. World J. Gastroenterol. 23, 1758-1763. https://doi.org/10.3748/wjg.v23.i10.1758

피인용 문헌

  1. Modulation of Type-I Interferon Response by hsa-miR-374b-5p During Japanese Encephalitis Virus Infection in Human Microglial Cells vol.9, pp.None, 2018, https://doi.org/10.3389/fcimb.2019.00291
  2. Analysis of the miRNA Expression Profiles in the Zearalenone-Exposed TM3 Leydig Cell Line vol.20, pp.3, 2018, https://doi.org/10.3390/ijms20030635
  3. Modulation of the IL-6-Signaling Pathway in Liver Cells by miRNAs Targeting gp130, JAK1, and/or STAT3 vol.16, pp.None, 2018, https://doi.org/10.1016/j.omtn.2019.03.007
  4. PTEN, A Target of Microrna-374b, Contributes to the Radiosensitivity of Canine Oral Melanoma Cells vol.20, pp.18, 2018, https://doi.org/10.3390/ijms20184631
  5. Long Non-Coding RNA MAGI2-AS3 is a New Player with a Tumor Suppressive Role in High Grade Serous Ovarian Carcinoma vol.11, pp.12, 2018, https://doi.org/10.3390/cancers11122008
  6. TWEAK promotes hepatic stellate cell migration through activating EGFR/Src and PI3K/AKT pathways vol.44, pp.1, 2018, https://doi.org/10.1002/cbin.11230
  7. Levosimendan Protects against Doxorubicin-Induced Cardiotoxicity by Regulating the PTEN/Akt Pathway vol.2020, pp.None, 2018, https://doi.org/10.1155/2020/8593617
  8. Genetic alterations in cell cycle regulation-associated genes may promote primary progression of gastrointestinal stromal tumors vol.100, pp.3, 2018, https://doi.org/10.1038/s41374-019-0322-x
  9. MicroRNA-498 inhibits the proliferation, migration and invasion of gastric cancer through targeting BMI-1 and suppressing AKT pathway vol.33, pp.2, 2020, https://doi.org/10.1007/s13577-019-00313-w
  10. HER4 promotes the growth and metastasis of osteosarcoma via the PI3K/AKT pathway vol.52, pp.4, 2018, https://doi.org/10.1093/abbs/gmaa004
  11. Dysregulation of miRNAs as a signature for diagnosis and prognosis of gastric cancer and their involvement in the mechanism underlying gastric carcinogenesis and progression vol.72, pp.5, 2018, https://doi.org/10.1002/iub.2259
  12. Role of PI3K/AKT pathway in cancer: the framework of malignant behavior vol.47, pp.6, 2018, https://doi.org/10.1007/s11033-020-05435-1
  13. MicroRNA ‐374b mediates the initiation of non‐small cell lung cancer by regulating ITGB1 and p53 expressions vol.11, pp.6, 2018, https://doi.org/10.1111/1759-7714.13457
  14. Role of non-coding RNAs in pathogenesis of gastrointestinal stromal tumors vol.8, pp.3, 2020, https://doi.org/10.13105/wjma.v8.i3.233
  15. PSMC6 promotes osteoblast apoptosis through inhibiting PI3K/AKT signaling pathway activation in ovariectomy‐induced osteoporosis mouse model vol.235, pp.7, 2020, https://doi.org/10.1002/jcp.29261
  16. miR‐4510 acts as a tumor suppressor in gastrointestinal stromal tumor by targeting APOC2 vol.235, pp.7, 2018, https://doi.org/10.1002/jcp.29506
  17. Identification of Novel microRNA Prognostic Markers Using Cascaded Wx, a Neural Network-Based Framework, in Lung Adenocarcinoma Patients vol.12, pp.7, 2018, https://doi.org/10.3390/cancers12071890
  18. Non-Coding RNAs, a Novel Paradigm for the Management of Gastrointestinal Stromal Tumors vol.21, pp.18, 2018, https://doi.org/10.3390/ijms21186975
  19. The Emerging Role of miRNAs for the Radiation Treatment of Pancreatic Cancer vol.12, pp.12, 2018, https://doi.org/10.3390/cancers12123703
  20. Global gene methylation profiling of common warts caused by human papillomaviruses infection vol.28, pp.1, 2018, https://doi.org/10.1016/j.sjbs.2020.10.050
  21. Systematic Analysis of Intronic miRNAs Reveals Cooperativity within the Multicomponent FTX Locus to Promote Colon Cancer Development vol.81, pp.5, 2018, https://doi.org/10.1158/0008-5472.can-20-1406
  22. Lithocholic Acid Induces miR21, Promoting PTEN Inhibition via STAT3 and ERK-1/2 Signaling in Colorectal Cancer Cells vol.22, pp.19, 2021, https://doi.org/10.3390/ijms221910209
  23. Tanshinone IIA combined with CsA inhibit myocardial cell apoptosis induced by renal ischemia-reperfusion injury in obese rats vol.21, pp.1, 2018, https://doi.org/10.1186/s12906-021-03270-w