Browse > Article
http://dx.doi.org/10.14348/molcells.2016.2336

Let-7c miRNA Inhibits the Proliferation and Migration of Heat-Denatured Dermal Fibroblasts Through Down-Regulating HSP70  

Jiang, Tao (Department of Vascular Surgery, China-Japan Union Hospital of Jilin University)
Wang, Xingang (Department of Burns and Plastic Surgery, China-Japan Union Hospital of Jilin University)
Wu, Weiwei (Department of Burns Surgery, the First Bethune Hospital of Jilin University)
Zhang, Fan (Center of Tuberculous Meningitis, Changchun City Hospital for Infectious Diseases)
Wu, Shifeng (Department of Burns and Plastic Surgery, China-Japan Union Hospital of Jilin University)
Publication Information
Molecules and Cells / v.39, no.4, 2016 , pp. 345-351 More about this Journal
Abstract
Wound healing is a complex physiological process necessitating the coordinated action of various cell types, signals and microRNAs (miRNAs). However, little is known regarding the role of miRNAs in mediating this process. In the present study, we show that let-7c miRNA is decreased in heat-denatured fibroblasts and that inhibiting let-7c expression leads to the increased proliferation and migration of dermal fibroblasts, whereas the overexpression of let-7c exerts an opposite effect. Further investigation has identified heat shock protein 70 as a direct target of let-7c and has demonstrated that the expression of HSP70 in fibroblasts is negatively correlated with let-7c levels. Moreover, down-regulation of let-7c expression is accompanied by up-regulation of Bcl-2 expression and down-regulation of Bax expression, both of which are the downstream genes of HSP70. Notably, the knockdown of HSP70 by HSP70 siRNA apparently abrogates the stimulatory effect of let-7c inhibitor on heat-denatured fibroblasts proliferation and migration. Overall, we have identified let-7c as a key regulator that inhibits fibroblasts proliferation and migration during wound healing.
Keywords
dermal fibroblast; heat; HSP70; Let-7c miRNA;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Barrientos, S., Stojadinovic, O., Golinko, M.S., Brem, H., and Tomic‐Canic, M. (2008). Growth factors and cytokines in wound healing. Wound Repair Regen. 16, 585-601.   DOI
2 Bartel, D.P. (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281-297.   DOI
3 Beere, H.M. (2004). "The stress of dying": the role of heat shock proteins in the regulation of apoptosis. J. Cell Sci. 117, 2641-2651.   DOI
4 Bjorner, S., Fitzpatrick, P.A., Li, Y., Allred, C., Howell, A., Ringberg, A., Olsson, H., Miller, C.J., Axelson, H., and Landberg, G. (2014). Epithelial and stromal microRNA signatures of columnar cell hyperplasia linking Let-7c to precancerous and cancerous breast cancer cell proliferation. PLoS One 9, e105099.   DOI
5 Calin, G.A., Sevignani, C., Dumitru, C.D., Hyslop, T., Noch, E., Yendamuri, S., Shimizu, M., Rattan, S., Bullrich, F., Negrini, M., et al. (2004). Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc. Natl. Acad. Sci. USA 101, 2999-3004.   DOI
6 Chen, P.Y., Qin, L., Barnes, C., Charisse, K., Yi, T., Zhang, X., Ali, R., Medina, P.P., Yu, J., Slack, F.J., et al. (2012). FGF regulates TGF-beta signaling and endothelial-to-mesenchymal transition via control of let-7 miRNA expression. Cell Rep. 2, 1684-1696.   DOI
7 Ciocca, D.R., and Calderwood, S.K. (2005). Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones 10, 86.   DOI
8 Clayton, A., Turkes, A., Navabi, H., Mason, M.D., and Tabi, Z. (2005). Induction of heat shock proteins in B-cell exosomes. J. Cell Sci. 118, 3631-3638.   DOI
9 De-quan, L., Xiao-yuan, H., and Xing-hua, Y. (2008). Morphology of human skin fibroblasts after heat injury in vitro. J. Clin. Rehabilitative Tissue Engineering Res. 12, 2056.
10 Felicetti, F., Errico, M.C., Bottero, L., Segnalini, P., Stoppacciaro, A., Biffoni, M., Felli, N., Mattia, G., Petrini, M., Colombo, M.P., et al. (2008). The promyelocytic leukemia zinc finger-microRNA-221/- 222 pathway controls melanoma progression through multiple oncogenic mechanisms. Cancer Res. 68, 2745-2754.   DOI
11 Hartl, F.U. (1996). Molecular chaperones in cellular protein folding. Nature 381, 571-579.   DOI
12 Huang, X., Yang, X., Lei, S., Xiao, M., Zhang, M., and Zeng, J. (2001). With the preservation of denatured dermis and autoskin grafting to repair of deeply burned hands. Zhonghua Shao Shang Za Zhi 17, 60-61.
13 Jego, G., Hazoume, A., Seigneuric, R., and Garrido, C. (2013). Targeting heat shock proteins in cancer. Cancer Lett. 332, 275-285.   DOI
14 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.   DOI
15 Li, D., Wang, A., Liu, X., Meisgen, F., Grunler, J., Botusan, I.R., Narayanan, S., Erikci, E., Li, X., Blomqvist, L., et al. (2015). MicroRNA-132 enhances transition from inflammation to proliferation during wound healing. J. Clin. Invest 125, 3008-3026.   DOI
16 Johnson, C.D., Esquela-Kerscher, A., Stefani, G., Byrom, M., Kelnar, K., Ovcharenko, D., Wilson, M., Wang, X., Shelton, J., and Shingara, J. (2007). The let-7 microRNA represses cell proliferation pathways in human cells. Cancer Res. 67, 7713-7722.   DOI
17 Kariya, A., Furusawa, Y., Yunoki, T., Kondo, T., and Tabuchi, Y. (2014). A microRNA-27a mimic sensitizes human oral squamous cell carcinoma HSC-4 cells to hyperthermia through downregulation of Hsp110 and Hsp90. Int. J. Mol. Med. 34, 334-340.   DOI
18 Koba, S., Jinnin, M., Inoue, K., Nakayama, W., Honda, N., Makino, K., Kajihara, I., Makino, T., Fukushima, S., and Ihn, H. (2013). Expression analysis of multiple microRNAs in each patient with scleroderma. Exp. Dermatol. 22, 489-491.   DOI
19 Liang, P., Lv, C., Jiang, B., Long, X., Zhang, P., Zhang, M., Xie, T., and Huang, X. (2012). MicroRNA profiling in denatured dermis of deep burn patients. Burns 38, 534-540.   DOI
20 Martin, P. (1997). Wound healing--aiming for perfect skin regeneration. Science 276, 75-81.   DOI
21 Motoyama, K., Inoue, H., Nakamura, Y., Uetake, H., Sugihara, K., and Mori, M. (2008). Clinical significance of high mobility group A2 in human gastric cancer and its relationship to let-7 microRNA family. Clin. Cancer Res. 14, 2334-2340.   DOI
22 Nadiminty, N., Tummala, R., Lou, W., Zhu, Y., Zhang, J., Chen, X., eVere White, R.W., Kung, H.J., Evans, C.P., and Gao, A.C. (2012). MicroRNA let-7c suppresses androgen receptor expression and activity via regulation of Myc expression in prostate cancer cells. J. Biol. Chem. 287, 1527-1537.   DOI
23 Reinke, J.M., and Sorg, H. (2012). Wound repair and regeneration. Eur. Surg. Res. 49, 35-43.   DOI
24 Nardai, G., Vegh, E.M., Prohaszka, Z., and Csermely, P. (2006). Chaperone-related immune dysfunction: an emergent property of distorted chaperone networks. Trends Immunol. 27, 74-79.   DOI
25 Pasquinelli, A.E., Reinhart, B.J., Slack, F., Martindale, M.Q., Kuroda, M.I., Maller, B., Hayward, D.C., Ball, E.E., Degnan, B., Muller, P., et al. (2000). Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature 408, 86-89.   DOI
26 Reinhart, B.J., Slack, F.J., Basson, M., Pasquinelli, A.E., Bettinger, J.C., Rougvie, A.E., Horvitz, H.R., and Ruvkun, G. (2000). The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403, 901-906.   DOI
27 Schmitt, E., Parcellier, A., Gurbuxani, S., Cande, C., Hammann, A., Morales, M.C., Hunt, C.R., Dix, D.J., Kroemer, R.T., Giordanetto, F., et al. (2003). Chemosensitization by a non-apoptogenic heat shock protein 70-binding apoptosis-inducing factor mutant. Cancer Res. 63, 8233-8240.
28 Schultz, J., Lorenz, P., Gross, G., Ibrahim, S., and Kunz, M. (2008). MicroRNA let-7b targets important cell cycle molecules in malignant melanoma cells and interferes with anchorageindependent growth. Cell Res. 18, 549-557.   DOI
29 Shin, J.U., Lee, W.J., Tran, T.N., Jung, I., and Lee, J.H. (2015). Hsp70 knockdown by siRNA decreased collagen production in keloid fibroblasts. Yonsei Med. J. 56, 1619-1626.   DOI
30 Singh, S., and Suri, A. (2014). Targeting the testis-specific heatshock protein 70-2 (HSP70-2) reduces cellular growth, migration, and invasion in renal cell carcinoma cells. Tumour Biol. 35, 12695-12706.   DOI
31 Yu, F., Yao, H., Zhu, P., Zhang, X., Pan, Q., Gong, C., Huang, Y., Hu, X., Su, F., and Lieberman, J. (2007). let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell 131, 1109-1123.   DOI
32 Stankiewicz, A.R., Lachapelle, G., Foo, C.P., Radicioni, S.M., and Mosser, D.D. (2005). Hsp70 inhibits heat-induced apoptosis upstream of mitochondria by preventing Bax translocation. J. Biol. Chem. 280, 38729-38739.   DOI
33 Wang, X., Chen, M., Zhou, J., and Zhang, X. (2014). HSP27, 70 and 90, anti-apoptotic proteins, in clinical cancer therapy (Review). Int. J. Oncol. 45, 18-30.   DOI
34 Yi, R., O'Carroll, D., Pasolli, H.A., Zhang, Z., Dietrich, F.S., Tarakhovsky, A., and Fuchs, E. (2006). Morphogenesis in skin is governed by discrete sets of differentially expressed microRNAs. Nat. Genet. 38, 356-362.   DOI
35 Zhao, B., Han, H., Chen, J., Zhang, Z., Li, S., Fang, F., Zheng, Q., Ma, Y., Zhang, J., Wu, N., and Yang, Y. (2014). MicroRNA let-7c inhibits migration and invasion of human non-small cell lung cancer by targeting ITGB3 and MAP4K3. Cancer Lett. 342, 43-51.   DOI
36 Zhu, X., Wu, L., Yao, J., Jiang, H., Wang, Q., Yang, Z. and Wu, F. (2015). MicroRNA let-7c inhibits cell proliferation and induces cell cycle arrest by targeting CDC25A in human hepatocellular carcinoma. PLoS One 10, e0124266.   DOI
37 Zylicz, M., King, F.W., and Wawrzynow, A. (2001). Hsp70 interactions with the p53 tumour suppressor protein. EMBO J. 20, 4634-4638.   DOI