MicroRNAs are involved in cervical cancer development, progression, clinical outcome and improvement treatment response (Review)
- Authors:
- Víctor González-Quintana
- Lizbeth Palma-Berré
- Alma D. Campos-Parra
- Eduardo López‑Urrutia
- Oscar Peralta-Zaragoza
- Rafael Vazquez-Romo
- Carlos Pérez-Plasencia
-
Affiliations: Cancer Genomics Laboratory, UBIMED, FES-Iztacala, UNAM, Los Reyes Iztacala, Tlalnepantla, México, Cancer Genomics Laboratory, National Cancer Institute of Mexico, Tlalpan, México, DF, México, Division of Chronic Infections and Cancer, Research Center for Infectious Diseases, INSP, Cuernavaca Morelos, México, Breast Cancer Surgery Department, National Cancer Institute of Mexico, Tlalpan, México, DF, México - Published online on: October 30, 2015 https://doi.org/10.3892/or.2015.4369
- Pages: 3-12
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|
Siegel R, Naishadham D and Jemal A: Cancer statistics for Hispanics/Latinos, 2012. CA Cancer J Clin. 62:283–298. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 127:2893–2917. 2010. View Article : Google Scholar | |
|
Serrano B, Alemany L, Ruiz PA, Tous S, Lima MA, Bruni L, Jain A, Clifford GM, Qiao YL, Weiss T, et al: Potential impact of a 9-valent HPV vaccine in HPV-related cervical disease in 4 emerging countries (Brazil, Mexico, India and China). Cancer Epidemiol. 38:748–756. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Landoni F, Maneo A, Colombo A, Placa F, Milani R, Perego P, Favini G, Ferri L and Mangioni C: Randomised study of radical surgery versus radiotherapy for stage Ib-IIa cervical cancer. Lancet. 350:535–540. 1997. View Article : Google Scholar : PubMed/NCBI | |
|
Quinn MA, Benedet JL, Odicino F, Maisonneuve P, Beller U, Creasman WT, Heintz AP, Ngan HY and Pecorelli S: Carcinoma of the cervix uteri. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. Int J Gynaecol Obstet. 95(Suppl 1): S43–S103. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Kong YW, Ferland-McCollough D, Jackson TJ and Bushell M: microRNAs in cancer management. Lancet Oncol. 13:e249–e258. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Suzuki H, Maruyama R, Yamamoto E and Kai M: Epigenetic alteration and microRNA dysregulation in cancer. Front Genet. 4:2582013. View Article : Google Scholar : PubMed/NCBI | |
|
Friedman RC, Farh KKH, Burge CB and Bartel DP: Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 19:92–105. 2009. View Article : Google Scholar : | |
|
Ma R, Jiang T and Kang X: Circulating microRNAs in cancer: Origin, function and application. J Exp Clin Cancer Res. 31:382012. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang B, Pan X, Cobb GP and Anderson TA: microRNAs as oncogenes and tumor suppressors. Dev Biol. 302:1–12. 2007. View Article : Google Scholar | |
|
Iorio MV and Croce CM: Causes and consequences of microRNA dysregulation. Cancer J. 18:215–222. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 6:857–866. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Agarwal SM, Raghav D, Singh H and Raghava GPS: CCDB: A curated database of genes involved in cervix cancer. Nucleic Acids Res. 39:D975–D979. 2011. View Article : Google Scholar : | |
|
Juan L, Tong HL, Zhang P, Guo G, Wang Z, Wen X, Dong Z and Tian YP: Identification and characterization of novel serum microRNA candidates from deep sequencing in cervical cancer patients. Sci Rep. 4:62772014. View Article : Google Scholar : PubMed/NCBI | |
|
Wang F, Li Y, Zhou J, Xu J, Peng C, Ye F, Shen Y, Lu W, Wan X and Xie X: miR-375 is down-regulated in squamous cervical cancer and inhibits cell migration and invasion via targeting transcription factor SP1. Am J Pathol. 179:2580–2588. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Kumar MS, Lu J, Mercer KL, Golub TR and Jacks T: Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet. 39:673–677. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Yao T and Lin Z: MiR-21 is involved in cervical squamous cell tumorigenesis and regulates CCL20. Biochim Biophys Acta. 1822:248–260. 2012. View Article : Google Scholar | |
|
Pang RTK, Leung CON, Ye TM, Liu W, Chiu PC, Lam KK, Lee KF and Yeung WS: MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells. Carcinogenesis. 31:1037–1044. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Li JH, Xiao X, Zhang YN, Wang YM, Feng LM, Wu YM and Zhang YX: MicroRNA miR-886-5p inhibits apoptosis by down-regulating Bax expression in human cervical carcinoma cells. Gynecol Oncol. 120:145–151. 2011. View Article : Google Scholar | |
|
Liu L, Yu X, Guo X, Tian Z, Su M, Long Y, Huang C, Zhou F, Liu M, Wu X, et al: miR-143 is downregulated in cervical cancer and promotes apoptosis and inhibits tumor formation by targeting Bcl-2. Mol Med Rep. 5:753–760. 2012. | |
|
Zhu X, Er K, Mao C, Yan Q, Xu H, Zhang Y, Zhu J, Cui F, Zhao W and Shi H: miR-203 suppresses tumor growth and angiogenesis by targeting VEGFA in cervical cancer. Cell Physiol Biochem. 32:64–73. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Lao G, Liu P, Wu Q, Zhang W, Liu Y, Yang L and Ma C: Mir-155 promotes cervical cancer cell proliferation through suppression of its target gene LKB1. Tumour Biol. 35:11933–11939. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Pereira PM, Marques JP, Soares AR, Carreto L and Santos MA: MicroRNA expression variability in human cervical tissues. PLoS One. 5:e117802010. View Article : Google Scholar : PubMed/NCBI | |
|
Li BH, Zhou JS, Ye F, Cheng XD, Zhou CY, Lu WG and Xie X: Reduced miR-100 expression in cervical cancer and precursors and its carcinogenic effect through targeting PLK1 protein. Eur J Cancer. 47:2166–2174. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Li Y, Wang F, Xu J, Ye F, Shen Y, Zhou J, Lu W, Wan X, Ma D and Xie X: Progressive miRNA expression profiles in cervical carcinogenesis and identification of HPV-related target genes for miR-29. J Pathol. 224:484–495. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Wang X, Meyers C, Guo M and Zheng ZM: Upregulation of p18Ink4c expression by oncogenic HPV E6 via p53-miR-34a pathway. Int J Cancer. 129:1362–1372. 2011. View Article : Google Scholar : | |
|
Lee JW, Choi CH, Choi JJ, Park YA, Kim SJ, Hwang SY, Kim WY, Kim TJ, Lee JH, Kim BG, et al: Altered MicroRNA expression in cervical carcinomas. Clin Cancer Res. 14:2535–2542. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration: Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: A systematic review and meta-analysis of individual patient data from 18 randomized trials. J Clin Oncol. 26:5802–5812. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Hu X, Schwarz JK, Lewis JS Jr, Huettner PC, Rader JS, Deasy JO, Grigsby PW and Wang X: A microRNA expression signature for cervical cancer prognosis. Cancer Res. 70:1441–1448. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Huang L, Lin JX, Yu YH, Zhang MY, Wang HY and Zheng M: Downregulation of six microRNAs is associated with advanced stage, lymph node metastasis and poor prognosis in small cell carcinoma of the cervix. PLoS One. 7:e337622012. View Article : Google Scholar : PubMed/NCBI | |
|
Shen SN, Wang LF, Jia YF, Hao YQ, Zhang L and Wang H: Upregulation of microRNA-224 is associated with aggressive progression and poor prognosis in human cervical cancer. Diagn Pathol. 8:692013. View Article : Google Scholar : PubMed/NCBI | |
|
Wang L, Wang Q, Li HL and Han LY: Expression of MiR200a, miR93, metastasis-related gene RECK and MMP2/MMP9 in human cervical carcinoma - relationship with prognosis. Asian Pac J Cancer Prev. 14:2113–2118. 2013. View Article : Google Scholar | |
|
Wang N, Zhou Y, Zheng L and Li H: MiR-31 is an independent prognostic factor and functions as an oncomir in cervical cancer via targeting ARID1A. Gynecol Oncol. 134:129–137. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Hu A, Huang JJ, Xu WH, Jin XJ, Li JP, Tang YJ, Huang XF, Cui HJ and Sun GB: miR-21 and miR-375 microRNAs as candidate diagnostic biomarkers in squamous cell carcinoma of the larynx: Association with patient survival. Am J Transl Res. 6:604–613. 2014.PubMed/NCBI | |
|
Miller P, Clarke J, Koru-Sengul T, Brinkman J and El-Ashry D: A novel MAPK-microRNA signature is predictive of hormone-therapy resistance and poor outcome in ER-positive breast cancer. Clin Cancer Res. 21:373–385. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Shi M, Du L, Liu D, Qian L, Hu M, Yu M, Yang Z, Zhao M, Chen C, Guo L, et al: Glucocorticoid regulation of a novel HPV-E6-p53-miR-145 pathway modulates invasion and therapy resistance of cervical cancer cells. J Pathol. 228:148–157. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Wang F, Liu M, Li X and Tang H: MiR-214 reduces cell survival and enhances cisplatin-induced cytotoxicity via down-regulation of Bcl2l2 in cervical cancer cells. FEBS Lett. 587:488–495. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang B, Chen J, Ren Z, Chen Y, Li J, Miao X, Song Y, Zhao T, Li Y, Shi Y, et al: A specific miRNA signature promotes radioresistance of human cervical cancer cells. Cancer Cell Int. 13:1182013. View Article : Google Scholar : PubMed/NCBI | |
|
Ke G, Liang L, Yang JM, Huang X, Han D, Huang S, Zhao Y, Zha R, He X and Wu X: MiR-181a confers resistance of cervical cancer to radiation therapy through targeting the pro-apoptotic PRKCD gene. Oncogene. 32:3019–3027. 2013. View Article : Google Scholar | |
|
Chen Y, Ke G, Han D, Liang S, Yang G and Wu X: MicroRNA-181a enhances the chemoresistance of human cervical squamous cell carcinoma to cisplatin by targeting PRKCD. Exp Cell Res. 320:12–20. 2014. View Article : Google Scholar | |
|
Fang L, Li H, Wang L, Hu J, Jin T, Wang J and Yang BB: MicroRNA-17-5p promotes chemotherapeutic drug resistance and tumour metastasis of colorectal cancer by repressing PTEN expression. Oncotarget. 5:2974–2987. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Lee KM, Choi EJ and Kim IA: microRNA-7 increases radiosen-sitivity of human cancer cells with activated EGFR-associated signaling. Radiother Oncol. 101:171–176. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Yang SM, Huang C, Li XF, Yu MZ, He Y and Li J: miR-21 confers cisplatin resistance in gastric cancer cells by regulating PTEN. Toxicology. 306:162–168. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Xie H, Lee L, Scicluna P, Kavak E, Larsson C, Sandberg R and Lui WO: Novel functions and targets of miR-944 in human cervical cancer cells. Int J Cancer. 136:E230–E241. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Villegas-Ruiz V, Juárez-Méndez S, Pérez-González OA, Arreola H, Paniagua-García L, Parra-Melquiadez M, Peralta-Rodríguez R, López-Romero R, Monroy-García A, Mantilla-Morales A, et al: Heterogeneity of microRNAs expression in cervical cancer cells: Over-expression of miR-196a. Int J Clin Exp Pathol. 7:1389–1401. 2014.PubMed/NCBI | |
|
Luo M, Shen D, Zhou X, Chen X and Wang W: MicroRNA-497 is a potential prognostic marker in human cervical cancer and functions as a tumor suppressor by targeting the insulin-like growth factor 1 receptor. Surgery. 153:836–847. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
He L, Wang HY, Zhang L, Huang L, Li JD, Xiong Y, Zhang MY, Jia WH, Yun JP, Luo RZ, et al: Prognostic significance of low DICER expression regulated by miR-130a in cervical cancer. Cell Death Dis. 5:e12052014. View Article : Google Scholar : PubMed/NCBI | |
|
Lei C, Wang Y, Huang Y, Yu H, Huang Y, Wu L and Huang L: Up-regulated miR155 reverses the epithelial-mesenchymal transition induced by EGF and increases chemo-sensitivity to cisplatin in human Caski cervical cancer cells. PLoS One. 7:e523102012. View Article : Google Scholar | |
|
Liang H, Li Y, Luo RY and Shen FJ: MicroRNA-215 is a potential prognostic marker for cervical cancer. J Huazhong Univ Sci Technolog Med Sci. 34:207–212. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Cai N, Wang YD and Zheng PS: The microRNA-302-367 cluster suppresses the proliferation of cervical carcinoma cells through the novel target AKT1. RNA. 19:85–95. 2013. View Article : Google Scholar : | |
|
Wang L, Chang L, Li Z, Gao Q, Cai D, Tian Y, Zeng L and Li M: miR-99a and -99b inhibit cervical cancer cell proliferation and invasion by targeting mTOR signaling pathway. Med Oncol. 31:9342014. View Article : Google Scholar : PubMed/NCBI | |
|
Xu J, Li Y, Wang F, Wang X, Cheng B, Ye F, Xie X, Zhou C and Lu W: Suppressed miR-424 expression via upregulation of target gene Chk1 contributes to the progression of cervical cancer. Oncogene. 32:976–987. 2013. View Article : Google Scholar | |
|
Wen SY, Lin Y, Yu YQ, Cao SJ, Zhang R, Yang XM, Li J, Zhang YL, Wang YH, Ma MZ, et al: miR-506 acts as a tumor suppressor by directly targeting the hedgehog pathway transcription factor Gli3 in human cervical cancer. Oncogene. 34:717–725. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Xie H, Zhao Y, Caramuta S, Larsson C and Lui WO: miR-205 expression promotes cell proliferation and migration of human cervical cancer cells. PLoS One. 7:e469902012. View Article : Google Scholar : PubMed/NCBI | |
|
Leung CON, Deng W, Ye T-M, Ngan HY, Tsao SW, Cheung AN, Pang RT and Yeung WS: miR-135a leads to cervical cancer cell transformation through regulation of β-catenin via a SIAH1-dependent ubiquitin proteosomal pathway. Carcinogenesis. 35:1931–1940. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Wei Q, Li Y-X, Liu M, Li X and Tang H: MiR-17-5p targets TP53INP1 and regulates cell proliferation and apoptosis of cervical cancer cells. IUBMB Life. 64:697–704. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang J, Li S, Yan Q, Chen X, Yang Y, Liu X and Wan X: Interferon-β induced microRNA-129-5p down-regulates HPV-18 E6 and E7 viral gene expression by targeting SP1 in cervical cancer cells. PLoS One. 8:e813662013. View Article : Google Scholar | |
|
Long MJ, Wu FX, Li P, Liu M, Li X and Tang H: MicroRNA-10a targets CHL1 and promotes cell growth, migration and invasion in human cervical cancer cells. Cancer Lett. 324:186–196. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Chu Y, Ouyang Y, Wang F, Zheng A, Bai L, Han L, Chen Y and Wang H: MicroRNA-590 promotes cervical cancer cell growth and invasion by targeting CHL1. J Cell Biochem. 115:847–853. 2014. View Article : Google Scholar | |
|
Xu XM, Wang XB, Chen MM, Liu T, Li YX, Jia WH, Liu M, Li X and Tang H: MicroRNA-19a and -19b regulate cervical carcinoma cell proliferation and invasion by targeting CUL5. Cancer Lett. 322:148–158. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Cui F, Li X, Zhu X, Huang L, Huang Y, Mao C, Yan Q, Zhu J, Zhao W and Shi H: MiR-125b inhibits tumor growth and promotes apoptosis of cervical cancer cells by targeting phosphoinositide 3-kinase catalytic subunit delta. Cell Physiol Biochem. 30:1310–1318. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Xin JX, Yue Z, Zhang S, Jiang ZH, Wang PY, Li YJ, Pang M and Xie SY: miR-99 inhibits cervical carcinoma cell proliferation by targeting TRIB2. Oncol Lett. 6:1025–1030. 2013.PubMed/NCBI | |
|
Kang HW, Wang F, Wei Q, Zhao YF, Liu M, Li X and Tang H: miR-20a promotes migration and invasion by regulating TNKS2 in human cervical cancer cells. FEBS Lett. 586:897–904. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang J, Zheng F, Yu G, Yin Y and Lu Q: miR-196a targets netrin 4 and regulates cell proliferation and migration of cervical cancer cells. Biochem Biophys Res Commun. 440:582–588. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Peng RQ, Wan HY, Li HF, Liu M, Li X and Tang H: MicroRNA-214 suppresses growth and invasiveness of cervical cancer cells by targeting UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 7. J Biol Chem. 287:14301–14309. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Wang YD, Cai N, Wu XL, Cao H-Z, Xie LL and Zheng PS: OCT4 promotes tumorigenesis and inhibits apoptosis of cervical cancer cells by miR-125b/BAK1 pathway. Cell Death Dis. 4:e7602013. View Article : Google Scholar : PubMed/NCBI | |
|
Qin W, Dong P, Ma C, Mitchelson K, Deng T, Zhang L, Sun Y, Feng X, Ding Y, Lu X, et al: MicroRNA-133b is a key promoter of cervical carcinoma development through the activation of the ERK and AKT1 pathways. Oncogene. 31:4067–4075. 2012. View Article : Google Scholar | |
|
How C, Hui ABY, Alajez NM, Shi W, Boutros PC, Clarke BA, Yan R, Pintilie M, Fyles A, Hedley DW, et al: MicroRNA-196b regulates the homeobox B7-vascular endothelial growth factor axis in cervical cancer. PLoS One. 8:e678462013. View Article : Google Scholar : PubMed/NCBI | |
|
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 | |
|
Yamamoto N, Kinoshita T, Nohata N, Itesako T, Yoshino H, Enokida H, Nakagawa M, Shozu M and Seki N: Tumor suppressive microRNA-218 inhibits cancer cell migration and invasion by targeting focal adhesion pathways in cervical squamous cell carcinoma. Int J Oncol. 42:1523–1532. 2013.PubMed/NCBI | |
|
Tian RQ, Wang XH, Hou LJ, Jia WH, Yang Q, Li YX, Liu M, Li X and Tang H: MicroRNA-372 is down-regulated and targets cyclin-dependent kinase 2 (CDK2) and cyclin A1 in human cervical cancer, which may contribute to tumorigenesis. J Biol Chem. 286:25556–25563. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Au Yeung CL, Tsang TY, Yau PL and Kwok TT: Human papillomavirus type 16 E6 induces cervical cancer cell migration through the p53/microRNA-23b/urokinase-type plasminogen activator pathway. Oncogene. 30:2401–2410. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Abdelmohsen K, Kim MM, Srikantan S, Mercken EM, Brennan SE, Wilson GM, Cabo R and Gorospe M: miR-519 suppresses tumor growth by reducing HuR levels. Cell Cycle. 9:1354–1359. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Qiang R, Wang F, Shi LY, Liu M, Chen S, Wan HY, Li YX, Li X, Gao SY and Sun BC: Plexin-B1 is a target of miR-214 in cervical cancer and promotes the growth and invasion of HeLa cells. Int J Biochem Cell Biol. 43:632–641. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Yao Q, Xu H, Zhang QQ, Zhou H and Qu LH: MicroRNA-21 promotes cell proliferation and down-regulates the expression of programmed cell death 4 (PDCD4) in HeLa cervical carcinoma cells. Biochem Biophys Res Commun. 388:539–542. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Li B, Hu Y, Ye F, Li Y, Lv W and Xie X: Reduced miR-34a expression in normal cervical tissues and cervical lesions with high-risk human papillomavirus infection. Int J Gynecol Cancer. 20:597–604. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Martinez I, Gardiner AS, Board KF, Monzon FA, Edwards RP and Khan SA: Human papillomavirus type 16 reduces the expression of microRNA-218 in cervical carcinoma cells. Oncogene. 27:2575–2582. 2008. View Article : Google Scholar : | |
|
Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, Vadas MA, Khew-Goodall Y and Goodall GJ: The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 10:593–601. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Melar-New M and Laimins LA: Human papillomaviruses modulate expression of microRNA 203 upon epithelial differentiation to control levels of p63 proteins. J Virol. 84:5212–5221. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Dong J, Sui L, Wang Q, Chen M and Sun H: MicroRNA-26a inhibits cell proliferation and invasion of cervical cancer cells by targeting protein tyrosine phosphatase type IVA 1. Mol Med Rep. 10:1426–1432. 2014.PubMed/NCBI |
