Analysis of the microRNA expression profile of normal human dermal papilla cells treated with 5α-dihydrotestosterone

Lee,Myung  Joo; Cha,Hwa  Jun; Lim,Kyung  Mi; Lee,Ok‑Kyu; Bae,Seunghee; Kim,Chun‑Ho; Lee,Kee‑Ho; Lee,Yu  Na; Ahn,Kyu  Joong; An,Sungkwan

doi:10.3892/mmr.2015.3478

Analysis of the microRNA expression profile of normal human dermal papilla cells treated with 5α-dihydrotestosterone

Authors:
- Myung Joo Lee
- Hwa Jun Cha
- Kyung Mi Lim
- Ok‑Kyu Lee
- Seunghee Bae
- Chun‑Ho Kim
- Kee‑Ho Lee
- Yu Na Lee
- Kyu Joong Ahn
- Sungkwan An
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Affiliations: Korea Institute for Skin and Clinical Sciences and Molecular‑Targeted Drug Research Center, Konkuk University, Seoul 143‑701, Republic of Korea, Korea Institute of Radiological and Medical Sciences, Seoul 139‑706, Republic of Korea, Department of Dermatology, Konkuk University School of Medicine, Seoul 143‑729, Republic of Korea
Published online on: March 12, 2015 https://doi.org/10.3892/mmr.2015.3478
Pages: 1205-1212

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Abstract

Clinical evidence has demonstrated that the accumulation of 5α‑dihydrotestosterone (DHT) in dermal papilla cells (DPCs) is implicated in androgenetic alopecia. Whether this accumulation in DHT may have direct cellular effects leading to androgenetic alopecia remains to be elucidated. The present study aimed to determine whether DHT affects cell growth, cell cycle arrest, cell death, senescence and the induction of reactive oxygen species (ROS), and whether these effects are mediated by microRNA (miRNA)‑dependent mechanisms. The cell viability and cell cycle were determined, levels of ROS were examined and senescence‑associated β‑galactosidase assays were performed in normal human DPCs (nHDPCs). Furthermore, miRNA expression profiling was performed using an miRNA microarray to determine whether changes in the expression levels of miRNA were associated with the cellular effects of DHT. The results revealed that DHT decreased cell growth by inducing cell death and G2 cell cycle arrest, and by increasing the production of ROS and senescence in the nHDPCs. In addition, 55 miRNAs were upregulated and 6 miRNAs were downregulated inthe DHT‑treated nHDPCs. Bioinformatic analysis demonstrated that the putative target genes of these upregulated and downregulated miRNAs were involved in cell growth, cell cycle arrest, cell death, senescence and the production of ROS. Specifically, the target genes of five highly upregulated and downregulated miRNAs were identified and were associated with the aforementioned effects of DHT. These results demonstrated that the expression of miRNA was altered in the DHT‑treated nHDPCs and suggest the potential mechanisms of DHT‑induced cell growth repression, cell cycle arrest, cell death, senescence and induction of ROS.

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1	Yazdan P: Update on the genetics of androgenetic alopecia, female pattern hair loss, and alopecia areata: Implications for molecular diagnostic testing. Semin Cutan Med Surg. 31:258–266. 2012. View Article : Google Scholar : PubMed/NCBI
2	Alsantali A and Shapiro J: Androgens and hair loss. Curr Opin Endocrinol Diabetes Obes. 16:246–253. 2009. View Article : Google Scholar : PubMed/NCBI
3	Canguven O and Burnett AL: The effect of 5 alpha-reductase inhibitors on erectile function. J Androl. 29:514–523. 2008. View Article : Google Scholar : PubMed/NCBI
4	Rove KO, Debruyne FM, Djavan B, Gomella LG, Koul HK, Lucia MS, Petrylak DP, Shore ND, Stone NN and Crawford ED: Role of testosterone in managing advanced prostate cancer. Urology. 80:754–762. 2012. View Article : Google Scholar : PubMed/NCBI
5	Hillier SG and Tetsuka M: Role of androgens in follicle maturation and atresia. Baillieres Clin Obstet Gynaecol. 11:249–260. 1997. View Article : Google Scholar : PubMed/NCBI
6	McElwee KJ, Kissling S, Wenzel E, Huth A and Hoffmann R: Cultured peribulbar dermal sheath cells can induce hair follicle development and contribute to the dermal sheath and dermal papilla. J Invest Dermatol. 121:1267–1275. 2003. View Article : Google Scholar : PubMed/NCBI
7	Yang CC and Cotsarelis G: Review of hair follicle dermal cells. J Dermatol Sci. 57:2–11. 2010. View Article : Google Scholar :
8	Tang L, Bernardo O, Bolduc C, Lui H, Madani S and Shapiro J: The expression of insulin-like growth factor 1 in follicular dermal papillae correlates with therapeutic efficacy of finasteride in androgenetic alopecia. J Am Acad Dermatol. 49:229–233. 2003. View Article : Google Scholar : PubMed/NCBI
9	Stenn KS, Combates NJ, Eilertsen KJ, Gordon JS, Pardinas JR, Parimoo S and Prouty SM: Hair follicle growth controls. Dermatol Clin. 14:543–558. 1996. View Article : Google Scholar : PubMed/NCBI
10	Peus D and Pittelkow MR: Growth factors in hair organ development and the hair growth cycle. Dermatol Clin. 14:559–572. 1996. View Article : Google Scholar : PubMed/NCBI
11	Stenn KS and Paus R: Controls of hair follicle cycling. Physiol Rev. 81:449–494. 2001.PubMed/NCBI
12	Ferraris C, Cooklis M, Polakowska RR and Haake AR: Induction of apoptosis through the PKC pathway in cultured dermal papilla fibroblasts. Exp Cell Res. 234:37–46. 1997. View Article : Google Scholar : PubMed/NCBI
13	Kwack MH, Sung YK, Chung EJ, Im SU, Ahn JS, Kim MK and Kim JC: Dihydrotestosterone-inducible dickkopf 1 from balding dermal papilla cells causes apoptosis in follicular keratinocytes. J Invest Dermatol. 128:262–269. 2008.
14	Winiarska A, Mandt N, Kamp H, Hossini A, Seltmann H, Zouboulis CC and Blume-Peytavi U: Effect of 5alpha-dihydrotestosterone and testosterone on apoptosis in human dermal papilla cells. Skin Pharmacol Physiol. 19:311–321. 2006. View Article : Google Scholar : PubMed/NCBI
15	Ambros V, Bartel B, Bartel DP, Burge CB, Carrington JC, Chen X, Dreyfuss G, Eddy SR, Griffiths-Jones S, Marshall M, et al: A uniform system for microRNA annotation. RNA. 9:277–279. 2003. View Article : Google Scholar : PubMed/NCBI
16	Valencia-Sanchez MA, Liu J, Hannon GJ and Parker R: Control of translation and mRNA degradation by miRNAs and siRNAs. Genes Dev. 20:515–524. 2006. View Article : Google Scholar : PubMed/NCBI
17	Ha TY: MicroRNAs in Human Diseases: From Cancer to Cardiovascular Disease. Immune Netw. 11:135–154. 2011. View Article : Google Scholar : PubMed/NCBI
18	Andl T, Murchison EP, Liu F, Zhang Y, Yunta-Gonzalez M, Tobias JW, Andl CD, Seykora JT, Hannon GJ and Millar SE: The miRNA-processing enzyme dicer is essential for the morphogenesis and maintenance of hair follicles. Curr Biol. 16:1041–1049. 2006. View Article : Google Scholar : PubMed/NCBI
19	Bae S, Lee EJ, Lee JH, Park IC, Lee SJ, Hahn HJ, Ahn KJ, An S, An IS and Cha HJ: Oridonin protects HaCaT keratinocytes against hydrogen peroxide-induced oxidative stress by altering microRNA expression. Int J Mol Med. 33:185–193. 2014.
20	Kim YJ, Cha HJ, Nam KH, Yoon Y, Lee H and An S: Centella asiatica extracts modulate hydrogen peroxide-induced senescence in human dermal fibroblasts. Exp Dermatol. 20:998–1003. 2011. View Article : Google Scholar : PubMed/NCBI
21	Simões VL, Alves MG, Martins AD, Dias TR, Rato L, Socorro S and Oliveira PF: Regulation of apoptotic signaling pathways by 5α-dihydrotestosterone and 17β-estradiol in immature rat Sertoli cells. J Steroid Biochem Mol Biol. 135:15–23. 2013. View Article : Google Scholar
22	Mirochnik Y, Veliceasa D, Williams L, Maxwell K, Yemelyanov A, Budunova I and Volpert OV: Androgen receptor drives cellular senescence. PLoS One. 7:e310522012. View Article : Google Scholar : PubMed/NCBI
23	Mehraein-Ghomi F, Lee E, Church DR, Thompson TA, Basu HS and Wilding G: JunD mediates androgen induced oxidative stress in androgen-dependent LNCaP human prostate cancer cells. Prostate. 68:924–934. 2008. View Article : Google Scholar : PubMed/NCBI
24	Ruizeveld de Winter JA, Trapman J, Vermey M, Mulder E, Zegers ND and van der Kwast TH: Androgen receptor expression in human tissues: An immunohistochemical study. J Histochem Cytochem. 39:927–936. 1991. View Article : Google Scholar : PubMed/NCBI
25	Takahashi A, Ohtani N, Yamakoshi K, Iida S, Tahara H, Nakayama K, Nakayama KI, Ide T, Saya H and Hara E: Mitogenic signalling and the p16INK4a-Rb pathway cooperate to enforce irreversible cellular senescence. Nat Cell Biol. 8:1291–1297. 2006. View Article : Google Scholar : PubMed/NCBI
26	Hodgins MB, Choudhry R, Parker G, Oliver RF, Jahoda CA, Withers AP, Brinkmann AO, van der Kwast TH, Boersma WJ, Lammers KM, et al: Androgen receptors in dermal papilla cells of scalp hair follicles in male pattern baldness. Ann NY Acad Sci. 642:448–451. 1991. View Article : Google Scholar : PubMed/NCBI
27	Eicheler W, Happle R and Hoffmann R: 5 alpha-reductase activity in the human hair follicle concentrates in the dermal papilla. Arch Dermatol Res. 290:126–132. 1998. View Article : Google Scholar : PubMed/NCBI
28	Trüeb RM: Molecular mechanisms of androgenetic alopecia. Exp Gerontol. 37:981–990. 2002. View Article : Google Scholar : PubMed/NCBI
29	Inui S and Itami S: Molecular basis of androgenetic alopecia: From androgen to paracrine mediators through dermal papilla. J Dermatol Sci. 61:1–6. 2011. View Article : Google Scholar
30	Mirochnik Y, Veliceasa D, Williams L, Maxwell K, Yemelyanov A, Budunova I and Volpert OV: Androgen receptor drives cellular senescence. PLoS One. 7:e310522012. View Article : Google Scholar : PubMed/NCBI
31	Colavitti R and Finkel T: Reactive oxygen species as mediators of cellular senescence. IUBMB Life. 57:277–281. 2005. View Article : Google Scholar : PubMed/NCBI
32	Ninio-Many L, Grossman H, Shomron N, Chuderland D and Shalgi R: microRNA-125a-3p reduces cell proliferation and migration by targeting Fyn. J Cell Sci. 126:2867–2876. 2013. View Article : Google Scholar : PubMed/NCBI
33	Anaya-Ruiz M, Bandala C and Perez-Santos JL: miR-485 acts as a tumor suppressor by inhibiting cell growth and migration in breast carcinoma T47D cells. Asian Pac J Cancer Prev. 14:3757–3760. 2013. View Article : Google Scholar : PubMed/NCBI
34	Wang Y, Liu J, Liu C, Naji A and Stoffers DA: MicroRNA-7 regulates the mTOR pathway and proliferation in adult pancreatic β-cells. Diabetes. 62:887–895. 2013. View Article : Google Scholar :
35	Fang Y, Xue JL, Shen Q, Chen J and Tian L: MicroRNA-7 inhibits tumor growth and metastasis by targeting the phosphoinositide 3-kinase/Akt pathway in hepatocellular carcinoma. Hepatology. 55:1852–1862. 2012. View Article : Google Scholar : PubMed/NCBI
36	Xiong S, Zheng Y, Jiang P, Liu R, Liu X and Chu Y: MicroRNA-7 inhibits the growth of human non-small cell lung cancer A549 cells through targeting BCL-2. Int J Biol Sci. 7:805–814. 2011. View Article : Google Scholar : PubMed/NCBI
37	Chou YT, Lin HH, Lien YC, Wang YH, Hong CF, Kao YR, Lin SC, Chang YC, Lin SY, Chen SJ, et al: EGFR promotes lung tumorigenesis by activating miR-7 through a Ras/ERK/Myc pathway that targets the Ets2 transcriptional repressor ERF. Cancer Res. 70:8822–8831. 2010. View Article : Google Scholar : PubMed/NCBI
38	Jiang L, Liu X, Chen Z, Jin Y, Heidbreder CE, Kolokythas A, Wang A, Dai Y and Zhou X: MicroRNA-7 targets IGF1R (insulin-like growth factor 1 receptor) in tongue squamous cell carcinoma cells. Biochem J. 432:199–205. 2010. View Article : Google Scholar : PubMed/NCBI
39	Liu S, Zhang P, Chen Z, Liu M, Li X and Tang H: MicroRNA-7 downregulates XIAP expression to suppress cell growth and promote apoptosis in cervical cancer cells. FEBS Lett. 587:2247–2253. 2013. View Article : Google Scholar : PubMed/NCBI