Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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LncRNA H19/miR-29b-3p/PGRN Axis Promoted Epithelial-Mesenchymal Transition of Colorectal Cancer Cells by Acting on Wnt Signaling

  • Ding, Dayong (Department of Gastrointestinal Surgery, China-Japan Union Hospital of Jilin University) ;
  • Li, Changfeng (Department of Endoscopy Center, China-Japan Union Hospital of Jilin University) ;
  • Zhao, Tiancheng (Department of Endoscopy Center, China-Japan Union Hospital of Jilin University) ;
  • Li, Dandan (Department of Endoscopy Center, China-Japan Union Hospital of Jilin University) ;
  • Yang, Lei (Department of Endoscopy Center, China-Japan Union Hospital of Jilin University) ;
  • Zhang, Bin (Department of Endoscopy Center, China-Japan Union Hospital of Jilin University)
  • Received : 2017.10.16
  • Accepted : 2018.01.14
  • Published : 2018.05.31
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Abstract

This investigation was aimed at working out the combined role of lncRNA H19, miR-29b and Wnt signaling in the development of colorectal cancer (CRC). In the aggregate, 185 CRC tissues and corresponding para-carcinoma tissues were gathered. The human CRC cell lines (i.e. HT29, HCT116, SW480 and SW620) and normal colorectal mucosa cell line (NCM460) were also purchased. Si-H19, si-NC, miR-29b-3p mimics, miR-29b-3p inhibitor, si-PGRN and negative control (NC) were, respectively, transfected into the CRC cells. Luciferase reporter plasmids were prepared to evaluate the transduction activity of $Wnt/{\beta}-catenin$ signaling pathway, and dual-luciferase reporter gene assay was arranged to confirm the targeted relationship between H19 and miR-29b-3p, as well as between miR-29b-3p and PGRN. Finally, the proliferative and invasive capacities of CRC cells were appraised through transwell, MTT and scratch assays. As a result, overexpressed H19 and down-expressed miR-29b-3p displayed close associations with the CRC patients' poor prognosis (P < 0.05). Besides, transfection with si-H19, miR-29b-3p mimic or si-PGRN were correlated with elevated E-cadherin expression, decreased snail and vimentin expressions, as well as less-motivated cell proliferation and cell metastasis (P < 0.05). Moreover, H19 was verified to directly target miR-29b-3p based on the luciferase reporter gene assay (P < 0.05), and miR-29b-3p also bound to PGRN in a direct manner (P < 0.05). Finally, addition of LiCl ($Wnt/{\beta}-catenin$ pathway activator) or XAV93920 ($Wnt/{\beta}-catenin$ pathway inhibitor) would cause remarkably altered E-cadherin, c-Myc, vimentin and snail expressions, as well as significantly changed transcriptional activity of ${\beta}-catenin/Tcf$ reporter plasmid (P < 0.05). In conclusion, the lncRNA H19/miR-29b-3p/PGRN/Wnt axis counted a great deal for seeking appropriate diagnostic biomarkers and treatment targets for CRC.

Keywords

References

  1. Chen, J., Li, Q., An, Y., Lv, N., Xue, X., Wei, J., Jiang, K., Wu, J., Gao, W., Qian, Z., et al. (2013). CEACAM6 induces epithelialmesenchymal transition and mediates invasion and metastasis in pancreatic cancer. Int. J. Oncol. 43, 877-885. https://doi.org/10.3892/ijo.2013.2015
  2. Chen, L., Li, Q., Wang, J., Jin, S., Zheng, H., Lin, J., He, F., Zhang, H., Ma, S., Mei, J., et al. (2017). MiR-29b-3p promotes chondrocyte apoptosis and facilitates the occurrence and development of osteoarthritis by targeting PGRN. J. Cell. Mol. Med. 21, 3347-3359. https://doi.org/10.1111/jcmm.13237
  3. Dong, T., Yang, D., Li, R., Zhang, L., Zhao, H., Shen, Y., Zhang, X., Kong, B., and Wang, L. (2016). PGRN promotes migration and invasion of epithelial ovarian cancer cells through an epithelial mesenchymal transition program and the activation of cancer associated fibroblasts. Exp. Mol. Pathol. 100, 17-25. https://doi.org/10.1016/j.yexmp.2015.11.021
  4. Dostie, J., Mourelatos, Z., Yang, M., Sharma, A., and Dreyfuss, G. (2003). Numerous microRNPs in neuronal cells containing novel microRNAs. RNA 9, 180-186. https://doi.org/10.1261/rna.2141503
  5. Fang, J.H., Zhou, H.C., Zeng, C., Yang, J., Liu, Y., Huang, X., Zhang, J.P., Guan, X.Y., and Zhuang, S.M. (2011). MicroRNA-29b suppresses tumor angiogenesis, invasion, and metastasis by regulating matrix metalloproteinase 2 expression. Hepatology 54, 1729-1740. https://doi.org/10.1002/hep.24577
  6. Gabory, A., Jammes, H., and Dandolo, L. (2010). The H19 locus: role of an imprinted non-coding RNA in growth and development. BioEssays 32, 473-480. https://doi.org/10.1002/bies.200900170
  7. Gillard, G., Shafaq-Zadah, M., Nicolle, O., Damaj, R., Pecreaux, J., and Michaux, G. (2015). Control of E-cadherin apical localisation and morphogenesis by a SOAP-1/AP-1/clathrin pathway in C. elegans epidermal cells. Development 142, 1684-1694. https://doi.org/10.1242/dev.118216
  8. Gnemmi, V., Bouillez, A., Gaudelot, K., Hemon, B., Ringot, B., Pottier, N., Glowacki, F., Villers, A., Vindrieux, D., Cauffiez, C., et al. (2014). MUC1 drives epithelial-mesenchymal transition in renal carcinoma through Wnt/beta-catenin pathway and interaction with SNAIL promoter. Cancer Lett. 346, 225-236. https://doi.org/10.1016/j.canlet.2013.12.029
  9. Gonzalez, D.M., and Medici, D. (2014). Signaling mechanisms of the epithelial-mesenchymal transition. Science Signal. 7, re8. https://doi.org/10.1126/scisignal.2005189
  10. Gupta, G.P., and Massague, J. (2006). Cancer metastasis: building a framework. Cell 127, 679-695. https://doi.org/10.1016/j.cell.2006.11.001
  11. Han, J., Rong, L.F., Shi, C.B., Dong, X.G., Wang, J., Wang, B.L., Wen, H., and He, Z.Y. (2014). Screening of lymph nodes metastasis associated lncRNAs in colorectal cancer patients. World J. Gastroenterol. 20, 8139-8150. https://doi.org/10.3748/wjg.v20.i25.8139
  12. Hardiman, K.M., Ulintz, P.J., Kuick, R.D., Hovelson, D.H., Gates, C.M., Bhasi, A., Rodrigues Grant, A., Liu, J., Cani, A.K., Greenson, J.K., et al. (2016). Intra-tumor genetic heterogeneity in rectal cancer. Lab Invest. 96, 4-15.
  13. Heiser, P.W., Lau, J., Taketo, M.M., Herrera, P.L., and Hebrok, M. (2006). Stabilization of beta-catenin impacts pancreas growth. Development 133, 2023-2032. https://doi.org/10.1242/dev.02366
  14. Heiser, P.W., Cano, D.A., Landsman, L., Kim, G.E., Kench, J.G., Klimstra, D.S., Taketo, M.M., Biankin, A.V., and Hebrok, M. (2008). Stabilization of beta-catenin induces pancreas tumor formation. Gastroenterology 135, 1288-1300. https://doi.org/10.1053/j.gastro.2008.06.089
  15. Huang, H., and He, X. (2008). Wnt/beta-catenin signaling: new (and old) players and new insights. Curr. Opin. Cell Biol. 20, 119-125. https://doi.org/10.1016/j.ceb.2008.01.009
  16. Hur, K., Toiyama, Y., Takahashi, M., Balaguer, F., Nagasaka, T., Koike, J., Hemmi, H., Koi, M., Boland, C.R., and Goel, A. (2013). MicroRNA-200c modulates epithelial-to-mesenchymal transition (EMT) in human colorectal cancer metastasis. Gut 62, 1315-1326. https://doi.org/10.1136/gutjnl-2011-301846
  17. Hwang, H.W., Wentzel, E.A., and Mendell, J.T. (2007). A hexanucleotide element directs microRNA nuclear import. Science 315, 97-100. https://doi.org/10.1126/science.1136235
  18. Katoh, M., and Katoh, M. (2007). WNT signaling pathway and stem cell signaling network. Clin. Cancer Res. 13, 4042-4045. https://doi.org/10.1158/1078-0432.CCR-06-2316
  19. Kogure, T., Kondo, Y., Kakazu, E., Ninomiya, M., Kimura, O., and Shimosegawa, T. (2014). Involvement of miRNA-29a in epigenetic regulation of transforming growth factor-beta-induced epithelialmesenchymal transition in hepatocellular carcinoma. Hepatol. Res. 44, 907-919. https://doi.org/10.1111/hepr.12188
  20. Lagos-Quintana, M., Rauhut, R., Lendeckel, W., and Tuschl, T. (2001). Identification of novel genes coding for small expressed RNAs. Science 294, 853-858. https://doi.org/10.1126/science.1064921
  21. Lagos-Quintana, M., Rauhut, R., Yalcin, A., Meyer, J., Lendeckel, W., and Tuschl, T. (2002). Identification of tissue-specific microRNAs from mouse. Curr. Biol. 12, 735-739.
  22. Li, H., Wang, Z., Zhang, W., Qian, K., Liao, G., Xu, W., and Zhang, S. (2015). VGLL4 inhibits EMT in part through suppressing Wnt/betacatenin signaling pathway in gastric cancer. Med. Oncol. 32, 83. https://doi.org/10.1007/s12032-015-0539-5
  23. Li, S., Hua, Y., Jin, J., Wang, H., Du, M., Zhu, L., Chu, H., Zhang, Z., and Wang, M. (2016). Association of genetic variants in lncRNA H19 with risk of colorectal cancer in a Chinese population. Oncotarget 7, 25470-25477.
  24. Liang, W.C., Fu, W.M., Wong, C.W., Wang, Y., Wang, W.M., Hu, G.X., Zhang, L., Xiao, L.J., Wan, D.C., Zhang, J.F., et al. (2015). The lncRNA H19 promotes epithelial to mesenchymal transition by functioning as miRNA sponges in colorectal cancer. Oncotarget 6, 22513-22525.
  25. Ling, H., Spizzo, R., Atlasi, Y., Nicoloso, M., Shimizu, M., Redis, R.S., Nishida, N., Gafa, R., Song, J., Guo, Z., et al. (2013). CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer. Genome Res. 23, 1446-1461. https://doi.org/10.1101/gr.152942.112
  26. Liu, L., Chen, L., Xu, Y., Li, R., and Du, X. (2010). microRNA-195 promotes apoptosis and suppresses tumorigenicity of human colorectal cancer cells. Biochem. Biophys. Res. Commun. 400, 236-240. https://doi.org/10.1016/j.bbrc.2010.08.046
  27. Liu, X., Yun, F., Shi, L., Li, Z.H., Luo, N.R., and Jia, Y.F. (2015). Roles of Signaling Pathways in the Epithelial-Mesenchymal Transition in Cancer. Asian Pac J Cancer Prev. 16, 6201-6206. https://doi.org/10.7314/APJCP.2015.16.15.6201
  28. Lu, Y.F., Liu, Y., Fu, W.M., Xu, J., Wang, B., Sun, Y.X., Wu, T.Y., Xu, L.L., Chan, K.M., Zhang, J.F., et al. (2017). Long noncoding RNA H19 accelerates tenogenic differentiation and promotes tendon healing through targeting miR-29b-3p and activating TGF-beta1 signaling. FASEB J. 31, 954-964. https://doi.org/10.1096/fj.201600722R
  29. Oft, M., Heider, K.H., and Beug, H. (1998). $TGF{\beta}$ signaling is necessary for carcinoma cell invasiveness and metastasis. Curr. Biol. 8, 1243-1252. https://doi.org/10.1016/S0960-9822(07)00533-7
  30. Pasca di Magliano, M., Biankin, A.V., Heiser, P.W., Cano, D.A., Gutierrez, P.J., Deramaudt, T., Segara, D., Dawson, A.C., Kench, J.G., Henshall, S.M., et al. (2007). Common activation of canonical Wnt signaling in pancreatic adenocarcinoma. PloS one 2, e1155. https://doi.org/10.1371/journal.pone.0001155
  31. Polyak, K., and Weinberg, R.A. (2009). Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat. Rev. Cancer 9, 265-273. https://doi.org/10.1038/nrc2620
  32. Poudyal, D., Cui, X., Le, P.M., Hofseth, A.B., Windust, A., Nagarkatti, M., Nagarkatti, P.S., Schetter, A.J., Harris, C.C., and Hofseth, L.J. (2013). A key role of microRNA-29b for the suppression of colon cancer cell migration by American ginseng. PloS one 8, e75034. https://doi.org/10.1371/journal.pone.0075034
  33. Prasad, C.P., Rath, G., Mathur, S., Bhatnagar, D., Parshad, R., and Ralhan, R. (2009). Expression analysis of E-cadherin, Slug and GSK3beta in invasive ductal carcinoma of breast. BMC Cancer 9, 325. https://doi.org/10.1186/1471-2407-9-325
  34. Shukla, G.C., Singh, J., and Barik, S. (2011). MicroRNAs: processing, maturation, target recognition and regulatory functions. Mol. Cell. Pharmacol. 3, 83-92.
  35. Siegel, R., Naishadham, D., and Jemal, A. (2012). Cancer statistics, 2012. CA Cancer J Clin. 62, 10-29. https://doi.org/10.3322/caac.20138
  36. Siegel, R., Desantis, C., and Jemal, A. (2014). Colorectal cancer statistics, 2014. CA Cancer J. Clin. 64, 104-117. https://doi.org/10.3322/caac.21220
  37. Slaby, O. (2016). Non-coding RNAs as biomarkers for colorectal cancer screening and early detection. Adv. Exp. Med. Biol. 937, 153-170.
  38. Subramanian, M., Rao, S.R., Thacker, P., Chatterjee, S., and Karunagaran, D. (2014). MiR-29b downregulates canonical Wnt signaling by suppressing coactivators of beta-catenin in human colorectal cancer cells. J. Cell. Biochem. 115, 1974-1984.
  39. Teng, Y., Zhao, L., Zhang, Y., Chen, W., and Li, X. (2014). Id-1, a protein repressed by miR-29b, facilitates the TGFbeta1-induced epithelial-mesenchymal transition in human ovarian cancer cells. Cell. Physiol. Biochem. 33, 717-730. https://doi.org/10.1159/000358647
  40. Thiery, J.P., Acloque, H., Huang, R.Y., and Nieto, M.A. (2009). Epithelial-mesenchymal transitions in development and disease. Cell 139, 871-890. https://doi.org/10.1016/j.cell.2009.11.007
  41. Thorvaldsen, J.L., Duran, K.L., and Bartolomei, M.S. (1998). Deletion of the H19 differentially methylated domain results in loss of imprinted expression of H19 and Igf2. Genes Dev. 12, 3693-3702. https://doi.org/10.1101/gad.12.23.3693
  42. Tian, R., Li, Y., and Yao, X. (2016). PGRN suppresses inflammation and promotes autophagy in keratinocytes through the Wnt/betacatenin signaling pathway. Inflammation 39, 1387-1394. https://doi.org/10.1007/s10753-016-0370-y
  43. Tsang, W.P., Ng, E.K., Ng, S.S., Jin, H., Yu, J., Sung, J.J., and Kwok, T.T. (2010). Oncofetal H19-derived miR-675 regulates tumor suppressor RB in human colorectal cancer. Carcinogenesis 31, 350-358. https://doi.org/10.1093/carcin/bgp181
  44. Tsuji, T., Ibaragi, S., and Hu, G.F. (2009). Epithelial-mesenchymal transition and cell cooperativity in metastasis. Cancer Res. 69, 7135-7139. https://doi.org/10.1158/0008-5472.CAN-09-1618
  45. Xie, X., Tang, B., Xiao, Y.F., Xie, R., Li, B.S., Dong, H., Zhou, J.Y., and Yang, S.M. (2016). Long non-coding RNAs in colorectal cancer. Oncotarget 7, 5226-5239.
  46. Xue, Y., Ma, G., Gu, D., Zhu, L., Hua, Q., Du, M., Chu, H., Tong, N., Chen, J., Zhang, Z., et al. (2015). Genome-wide analysis of long noncoding RNA signature in human colorectal cancer. Gene 556, 227-234. https://doi.org/10.1016/j.gene.2014.11.060
  47. Yamakuchi, M., Ferlito, M., and Lowenstein, C.J. (2008). miR-34a repression of SIRT1 regulates apoptosis. Proc. Natl. Acad. Sci. USA 105, 13421-13426. https://doi.org/10.1073/pnas.0801613105
  48. Ye, J., Wu, X., Wu, D., Wu, P., Ni, C., Zhang, Z., Chen, Z., Qiu, F., Xu, J., and Huang, J. (2013). miRNA-27b targets vascular endothelial growth factor C to inhibit tumor progression and angiogenesis in colorectal cancer. PloS one 8, e60687. https://doi.org/10.1371/journal.pone.0060687
  49. Yu, Y., Kanwar, S.S., Patel, B.B., Oh, P.S., Nautiyal, J., Sarkar, F.H., and Majumdar, A.P. (2012). MicroRNA-21 induces stemness by downregulating transforming growth factor beta receptor 2 (TGFbetaR2) in colon cancer cells. Carcinogenesis 33, 68-76. https://doi.org/10.1093/carcin/bgr246
  50. Zhai, Z., Yu, X., Yang, B., Zhang, Y., Zhang, L., Li, X., and Sun, H. (2017). Colorectal cancer heterogeneity and targeted therapy: Clinical implications, challenges and solutions for treatment resistance. Semin. Cell Dev. Biol. 64, 107-115. https://doi.org/10.1016/j.semcdb.2016.08.033
  51. Zhang, Y., Morris, J.P.t., Yan, W., Schofield, H.K., Gurney, A., Simeone, D.M., Millar, S.E., Hoey, T., Hebrok, M., and Pasca di Magliano, M. (2013). Canonical wnt signaling is required for pancreatic carcinogenesis. Cancer Res. 73, 4909-4922. https://doi.org/10.1158/0008-5472.CAN-12-4384
  52. Zhou, Y., Liang, C., Xue, F., Chen, W., Zhi, X., Feng, X., Bai, X., and Liang, T. (2015). Salinomycin decreases doxorubicin resistance in hepatocellular carcinoma cells by inhibiting the beta-catenin/TCF complex association via FOXO3a activation. Oncotarget 6, 10350-10365.

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  48. LncRNA signature in colorectal cancer vol.222, pp.None, 2018, https://doi.org/10.1016/j.prp.2021.153432
  49. miRNA Clusters with Up-Regulated Expression in Colorectal Cancer vol.13, pp.12, 2021, https://doi.org/10.3390/cancers13122979
  50. Noncoding RNAs as Promising Diagnostic Biomarkers and Therapeutic Targets in Intestinal Fibrosis of Crohn’s Disease: The Path From Bench to Bedside vol.27, pp.7, 2018, https://doi.org/10.1093/ibd/izaa321
  51. Identification and Roles of miR-29b-1-3p and miR29a-3p-Regulated and Non-Regulated lncRNAs in Endocrine-Sensitive and Resistant Breast Cancer Cells vol.13, pp.14, 2021, https://doi.org/10.3390/cancers13143530
  52. LINC00174 Facilitates Proliferation and Migration of Colorectal Cancer Cells via MiR-3127-5p/ E2F7 Axis vol.31, pp.8, 2018, https://doi.org/10.4014/jmb.2103.03001
  53. A New Light on Potential Therapeutic Targets for Colorectal Cancer Treatment vol.9, pp.10, 2018, https://doi.org/10.3390/biomedicines9101438
  54. Comprehensive analysis of ceRNA networks reveals prognostic lncRNAs related to immune infiltration in colorectal cancer vol.21, pp.1, 2021, https://doi.org/10.1186/s12885-021-07995-2
  55. LINC00963 affects the development of colorectal cancer via MiR-532-3p/HMGA2 axis vol.21, pp.1, 2018, https://doi.org/10.1186/s12935-020-01706-w
  56. Prognostic value and immune infiltration of novel signatures in colon cancer microenvironment vol.21, pp.1, 2021, https://doi.org/10.1186/s12935-021-02342-8
  57. Increased Expression of Long Non-coding RNA H19 is Associated With Colon Cancer Recurrence vol.269, pp.None, 2018, https://doi.org/10.1016/j.jss.2021.08.004