Single-cell transcriptomics reveals cell type diversity of human prostate

Yang Chen; Peng Zhang; Jinling Liao; Jiwen Cheng; Qin Zhang; Tianyu Li; Haiying Zhang; Yonghua Jiang; Fangxing Zhang; Yanyu Zeng; Linjian Mo; Haibiao Yan; Deyun Liu; Qinyun Zhang; Chunlin Zou; Gong-Hong Wei; Zengnan Mo

doi:10.1016/j.jgg.2022.03.009

Volume 49 Issue 11

Nov. 2022

Turn off MathJax

Article Contents

Article Navigation > Journal of Genetics and Genomics > 2022 > 49(11): 1002-1015

PDF( 5628 KB)

Single-cell transcriptomics reveals cell type diversity of human prostate

doi: 10.1016/j.jgg.2022.03.009

a. Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi 530021, China;
b. Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China;
c. Key Laboratory of Metabolism and Molecular Medicine of the Ministry of Education & Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 201114, China;
d. Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland;
e. Key Laboratory of Longevity and Ageing-Related Disease of Chinese Ministry of Education, Center for Translational Medicine and School of Preclinical Medicine, Guangxi Medical University, Nanning, Guangxi 530021, China

Funds:

This study was funded by the Youth Science Foundation of Guangxi Medical University (GXMUYSF201810), the National Natural Science Foundation of China (81901538, 81670750, 81770759), the Sigrid Jusélius Foundation and the Recruitment Fund of Fudan University, the National Key Research and Development Program of China (2017YFC0908000), the Major Project of Guangxi Innovation Driven (AA18118016), and the Guangxi Key Laboratory for Genomic and Personalized Medicine (16-380-54, 17-259-45, 19-050-22, 19-185-33, and 20-065-33).

Received Date: 2021-11-28
Accepted Date: 2022-03-16
Rev Recd Date: 2022-03-06
Publish Date: 2022-04-06

Abstract

Abstract

Extensive studies have been performed to describe the phenotypic changes occurring during malignant transformation of the prostate. However, the cell types and associated changes that contribute to the development of prostate diseases and cancer remain elusive, largely due to the heterogeneous composition of prostatic tissues. Here, we conduct a comprehensive evaluation of four human prostate tissues by single-cell RNA sequencing (scRNA-seq) to analyze their cellular compositions. We identify 18 clusters of cell types, each with distinct gene expression profiles and unique features; of these, one cluster of epithelial cells (Ep) is found to be associated with immune function. In addition, we characterize a special cluster of fibroblasts and aberrant signaling changes associated with prostate cancer (PCa). Moreover, we provide insights into the epithelial changes that occur during the cellular senescence and aging. These results expand our understanding of the unique functional associations between the diverse prostatic cell types and the contributions of specific cell clusters to the malignant transformation of prostate tissues and PCa development.
- scRNA-seq,
- Human prostate,
- Cell type diversity,
- Immunity,
- Cellular senescence,
- Prostate cancer

FullText(HTML)

References(71)

References

Apanovich, N., Peters, M., Apanovich, P., Mansorunov, D., Markova, A., Matveev, V., Karpukhin, A., 2020. The Genes-Candidates for Prognostic Markers of Metastasis by Expression Level in Clear Cell Renal Cell Cancer. Diagnostics (Basel) 10(1)

Azizi, E., Carr, A.J., Plitas, G., Cornish, A.E., Konopacki, C., Prabhakaran, S., Nainys, J., Wu, K., Kiseliovas, V., Setty, M., Choi, K., Fromme, R.M., Dao, P., McKenney, P.T., Wasti, R.C., Kadaveru, K., Mazutis, L., Rudensky, A.Y., Pe'er, D., 2018. Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment. Cell 174, 1293-1308 e1236

Barrett, T., Wilhite, S.E., Ledoux, P., Evangelista, C., Kim, I.F., Tomashevsky, M., Marshall, K.A., Phillippy, K.H., Sherman, P.M., Holko, M., Yefanov, A., Lee, H., Zhang, N., Robertson, C.L., Serova, N., Davis, S., Soboleva, A., 2013. NCBI GEO: archive for functional genomics data sets--update. Nucleic Acids Res. 41(Database issue), D991-995

Campbell, C.L., Jiang, Z., Savarese, D.M., Savarese, T.M., 2001. Increased expression of the interleukin-11 receptor and evidence of STAT3 activation in prostate carcinoma. Am J Pathol 158, 25-32

Campisi, J., 2013. Aging, cellular senescence, and cancer. Annu. Rev. Physiol. 75, 685-705

Cerami, E., Gao, J., Dogrusoz, U., Gross, B.E., Sumer, S.O., Aksoy, B.A., Jacobsen, A., Byrne, C.J., Heuer, M.L., Larsson, E., Antipin, Y., Reva, B., Goldberg, A.P., Sander, C., Schultz, N., 2012. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2, 401-404

Chen, S., Zhu, G., Yang, Y., Wang, F., Xiao, Y.T., Zhang, N., Bian, X., Zhu, Y., Yu, Y., Liu, F., Dong, K., Mariscal, J., Liu, Y., Soares, F., Loo Yau, H., Zhang, B., Chen, W., Wang, C., Chen, D., Guo, Q., Yi, Z., Liu, M., Fraser, M., De Carvalho, D.D., Boutros, P.C., Di Vizio, D., Jiang, Z., van der Kwast, T., Berlin, A., Wu, S., Wang, J., He, H.H., Ren, S., 2021. Single-cell analysis reveals transcriptomic remodellings in distinct cell types that contribute to human prostate cancer progression. Nat. Cell Biol. 23, 87-98

Cheng, Y., Chen, Y., Li, X., Wang, X., Chen, J., Wang, Z., Xu, B., 2017. Loss of Sun2 promotes the progression of prostate cancer by regulating fatty acid oxidation. Oncotarget 8, 89620e89630

Chesney, J., Bacher, M., Bender, A., Bucala, R., 1997. The peripheral blood fibrocyte is a potent antigen-presenting cell capable of priming naive T cells in situ. Proc. Natl. Acad. Sci. U S A. 94, 6307-6312

Choi, J., Shendrik, I., Peacocke, M., Peehl, D., Buttyan, R., Ikeguchi, E.F., Katz, A.E., Benson, M.C., 2000. Expression of senescence-associated beta-galactosidase in enlarged prostates from men with benign prostatic hyperplasia. Urology 56, 160-166

Coppe, J.P., Patil, C.K., Rodier, F., Sun, Y., Munoz, D.P., Goldstein, J., Nelson, P.S., Desprez, P.Y., Campisi, J., 2008. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. 6, 2853-2868

Crowell, P.D., Fox, J.J., Hashimoto, T., Diaz, J.A., Navarro, H.I., Henry, G.H., Feldmar, B.A., Lowe, M.G., Garcia, A.J., Wu, Y.E., Sajed, D.P., Strand, D.W., Goldstein, A.S., 2019. Expansion of Luminal Progenitor Cells in the Aging Mouse and Human Prostate. Cell Rep. 28, 1499-1510

Dahlman, A., Rexhepaj, E., Brennan, D.J., Gallagher, W.M., Gaber, A., Lindgren, A., Jirstrom, K., Bjartell, A., 2011. Evaluation of the prognostic significance of MSMB and CRISP3 in prostate cancer using automated image analysis. Mod. Pathol. 24, 708-719

De Buck, M., Gouwy, M., Wang, J.M., Van Snick, J., Opdenakker, G., Struyf, S., Van Damme, J., 2016. Structure and Expression of Different Serum Amyloid A (SAA) Variants and their Concentration-Dependent Functions During Host Insults. Curr. Med. Chem. 23, 1725-1755

de Kok, J.B., Verhaegh, G.W., Roelofs, R.W., Hessels, D., Kiemeney, L.A., Aalders, T.W., Swinkels, D.W., Schalken, J.A., 2002. DD3(PCA3), a very sensitive and specific marker to detect prostate tumors. Cancer Res. 62, 2695-2698

Dimri, G.P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E.E., Linskens, M., Rubelj, I., Pereira-Smith, O., et al., 1995. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc. Natl. Acad. Sci. U S A. 92, 9363-9367

Dong, B., Miao, J., Wang, Y., Luo, W., Ji, Z., Lai, H., Zhang, M., Cheng, X., Wang, J., Fang, Y., Zhu, H.H., Chua, C.W., Fan, L., Zhu, Y., Pan, J., Wang, J., Xue, W., Gao, W.Q., 2020. Single-cell analysis supports a luminal-neuroendocrine transdifferentiation in human prostate cancer. Commun. Biol. 3, 778

Dy, G.W., Gore, J.L., Forouzanfar, M.H., Naghavi, M., Fitzmaurice, C., 2017. Global Burden of Urologic Cancers, 1990-2013. Eur. Urol. 71, 437-446

EAU, 2018. EAU Guidelines. Edn. presented at the EAU Annual Congress Copenhagen 2018. ISBN 978-94-92671-01-1

Edgar, R., Domrachev, M., Lash, A.E., 2002. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 30, 207-210

Feng, P., Li, T., Guan, Z., Franklin, R.B., Costello, L.C., 2008. The involvement of Bax in zinc-induced mitochondrial apoptogenesis in malignant prostate cells. Mol. Cancer 7, 25

Franz, M.C., Anderle, P., Burzle, M., Suzuki, Y., Freeman, M.R., Hediger, M.A., Kovacs, G., 2013. Zinc transporters in prostate cancer. Mol. Aspects. Med. 34, 735-741

Furuya, Y., Sekine, Y., Kato, H., Miyazawa, Y., Koike, H., Suzuki, K., 2016. Low-density lipoprotein receptors play an important role in the inhibition of prostate cancer cell proliferation by statins. Prostate Int. 4, 56-60

Gao, Q., Zheng, J., 2018. Ginsenoside Rh2 inhibits prostate cancer cell growth through suppression of microRNA-4295 that activates CDKN1A. Cell Prolif. 51, e12438

Grasso, C.S., Wu, Y.M., Robinson, D.R., Cao, X., Dhanasekaran, S.M., Khan, A.P., Quist, M.J., Jing, X., Lonigro, R.J., Brenner, J.C., Asangani, I.A., Ateeq, B., Chun, S.Y., Siddiqui, J., Sam, L., Anstett, M., Mehra, R., Prensner, J.R., Palanisamy, N., Ryslik, G.A., Vandin, F., Raphael, B.J., Kunju, L.P., Rhodes, D.R., Pienta, K.J., Chinnaiyan, A.M., Tomlins, S.A., 2012. The mutational landscape of lethal castration-resistant prostate cancer. Nature 487, 239-243

Guo, W., Li, L., He, J., Liu, Z., Han, M., Li, F., Xia, X., Zhang, X., Zhu, Y., Wei, Y., Li, Y., Aji, R., Dai, H., Wei, H., Li, C., Chen, Y., Chen, L., Gao, D., 2020. Single-cell transcriptomics identifies a distinct luminal progenitor cell type in distal prostate invagination tips. Nat. Genet. 52, 908-918

Henry, G.H., Malewska, A., Joseph, D.B., Malladi, V.S., Lee, J., Torrealba, J., Mauck, R.J., Gahan, J.C., Raj, G.V., Roehrborn, C.G., Hon, G.C., MacConmara, M.P., Reese, J.C., Hutchinson, R.C., Vezina, C.M., Strand, D.W., 2018. A Cellular Anatomy of the Normal Adult Human Prostate and Prostatic Urethra. Cell Rep. 25, 3530-3542

Hessels, D., Klein Gunnewiek, J.M., van Oort, I., Karthaus, H.F., van Leenders, G.J., van Balken, B., Kiemeney, L.A., Witjes, J.A., Schalken, J.A., 2003. DD3(PCA3)-based molecular urine analysis for the diagnosis of prostate cancer. Eur. Urol. 44, 8-15

Hinrichs, B.H., Matthews, J.D., Siuda, D., O'Leary, M.N., Wolfarth, A.A., Saeedi, B.J., Nusrat, A., Neish, A.S., 2018. Serum Amyloid A1 Is an Epithelial Prorestitutive Factor. Am. J. Pathol. 188, 937-949

Hou, Q., Bing, Z.T., Hu, C., Li, M.Y., Yang, K.H., Mo, Z., Xie, X.W., Liao, J.L., Lu, Y., Horie, S., Lou, M.W., 2018. RankProd Combined with Genetic Algorithm Optimized Artificial Neural Network Establishes a Diagnostic and Prognostic Prediction Model that Revealed C1QTNF3 as a Biomarker for Prostate Cancer. EBioMedicine 32, 234-244

Hrvatin, S., Hochbaum, D.R., Nagy, M.A., Cicconet, M., Robertson, K., Cheadle, L., Zilionis, R., Ratner, A., Borges-Monroy, R., Klein, A.M., Sabatini, B.L., Greenberg, M.E., 2018. Single-cell analysis of experience-dependent transcriptomic states in the mouse visual cortex. Nat. Neurosci. 21, 120-129

Hutton, A.J., Polak, M.E., Spalluto, C.M., Wallington, J.C., Pickard, C., Staples, K.J., Warner, J.A., Wilkinson, T.M., 2017. Human Lung Fibroblasts Present Bacterial Antigens to Autologous Lung Th Cells. J. Immunol. 198, 110-118

Igarashi, T., Inatomi, J., Sekine, T., Cha, S.H., Kanai, Y., Kunimi, M., Tsukamoto, K., Satoh, H., Shimadzu, M., Tozawa, F., Mori, T., Shiobara, M., Seki, G., Endou, H., 1999. Mutations in SLC4A4 cause permanent isolated proximal renal tubular acidosis with ocular abnormalities. Nat. Genet. 23, 264-266

Jalava, S.E., Urbanucci, A., Latonen, L., Waltering, K.K., Sahu, B., Janne, O.A., Seppala, J., Lahdesmaki, H., Tammela, T.L., Visakorpi, T., 2012. Androgen-regulated miR-32 targets BTG2 and is overexpressed in castration-resistant prostate cancer. Oncogene 31, 4460-4471

Khorasani, M., Shahbazi, S., Hosseinkhan, N., Mahdian, R., 2019. Analysis of Differential Expression of microRNAs and Their Target Genes in Prostate Cancer: A Bioinformatics Study on Microarray Gene Expression Data. Int. J. Mol .Cell Med. 8, 103-114

Kolenko, V., Teper, E., Kutikov, A., Uzzo, R., 2013. Zinc and zinc transporters in prostate carcinogenesis. Nat. Rev. Urol. 10, 219-226

Kolfschoten, I.G., van Leeuwen, B., Berns, K., Mullenders, J., Beijersbergen, R.L., Bernards, R., Voorhoeve, P.M., Agami, R., 2005. A genetic screen identifies PITX1 as a suppressor of RAS activity and tumorigenicity. Cell 121, 849-858

Liu, Q., Li, E., Huang, L., Cheng, M., Li, L., 2018. Limb-bud and Heart Overexpression Inhibits the Proliferation and Migration of PC3M Cells. J. Cancer 9, 424-432

Liu, X., Gomez-Pinillos, A., Loder, C., Carrillo-de Santa Pau, E., Qiao, R., Unger, P.D., Kurek, R., Oddoux, C., Melamed, J., Gallagher, R.E., Mandeli, J., Ferrari, A.C., 2012. KLF6 loss of function in human prostate cancer progression is implicated in resistance to androgen deprivation. Am. J. Pathol. 181, 1007-1016

Ma, X., Guo, J., Liu, K., Chen, L., Liu, D., Dong, S., Xia, J., Long, Q., Yue, Y., Zhao, P., Hu, F., Xiao, Z., Pan, X., Xiao, K., Cheng, Z., Ke, Z., Chen, Z.S., Zou, C., 2020. Identification of a distinct luminal subgroup diagnosing and stratifying early stage prostate cancer by tissue-based single-cell RNA sequencing. Mol. Cancer 19, 147

Mariotti, S., Sargentini, V., Pardini, M., Giannoni, F., De Spirito, M., Gagliardi, M.C., Greco, E., Teloni, R., Fraziano, M., Nisini, R., 2013. Mycobacterium tuberculosis may escape helper T cell recognition by infecting human fibroblasts. Hum. Immunol. 74, 722-729

Memari, N., Diamandis, E.P., Earle, T., Campbell, A., Van Dekken, H., Van der Kwast, T.H., 2007. Human kallikrein-related peptidase 12: antibody generation and immunohistochemical localization in prostatic tissues. Prostate 67, 1465-1474

Ni, W.D., Yang, Z.T., Cui, C.A., Cui, Y., Fang, L.Y., Xuan, Y.H., 2017. Tenascin-C is a potential cancer-associated fibroblasts marker and predicts poor prognosis in prostate cancer. Biochem. Biophys. Res. Commun. 486, 607-612

Niccoli, T., Partridge, L., 2012. Ageing as a risk factor for disease. Curr. Biol. 22, R741-752

Nyambo, R., Cross, N., Lippitt, J., Holen, I., Bryden, G., Hamdy, F.C., Eaton, C.L., 2004. Human bone marrow stromal cells protect prostate cancer cells from TRAIL-induced apoptosis. J. Bone. Miner. Res. 19, 1712-1721

O'Malley, K.J., Dhir, R., Nelson, J.B., Bost, J., Lin, Y., Wang, Z., 2009. The expression of androgen-responsive genes is up-regulated in the epithelia of benign prostatic hyperplasia. Prostate 69, 1716-1723

Parks, S.K., Chiche, J., Pouyssegur, J., 2013. Disrupting proton dynamics and energy metabolism for cancer therapy. Nat. Rev. Cancer 13, 611-623

Parks, S.K., Pouyssegur, J., 2015. The Na(+)/HCO3(-) Co-Transporter SLC4A4 Plays a Role in Growth and Migration of Colon and Breast Cancer Cells. J. Cell Physiol. 230, 1954-1963

Penticuff, J.C., Woolbright, B.L., Sielecki, T.M., Weir, S.J., Taylor, J.A., 3rd, 2019. MIF family proteins in genitourinary cancer: tumorigenic roles and therapeutic potential. Nat. Rev. Urol. 16, 318-328

Qian, X., Li, C., Pang, B., Xue, M., Wang, J., Zhou, J., 2012. Spondin-2 (SPON2), a more prostate-cancer-specific diagnostic biomarker. PLoS One 7, e37225

Qiu, X., Mao, Q., Tang, Y., Wang, L., Chawla, R., Pliner, H.A., Trapnell, C., 2017. Reversed graph embedding resolves complex single-cell trajectories. Nat. Methods 14, 979-982

Ramilowski, J.A., Goldberg, T., Harshbarger, J., Kloppmann, E., Lizio, M., Satagopam, V.P., Itoh, M., Kawaji, H., Carninci, P., Rost, B., Forrest, A.R., 2015. A draft network of ligand-receptor-mediated multicellular signalling in human. Nat. Commun. 6, 7866

Rhodes, D.R., Yu, J., Shanker, K., Deshpande, N., Varambally, R., Ghosh, D., Barrette, T., Pandey, A., Chinnaiyan, A.M., 2004. ONCOMINE: a cancer microarray database and integrated data-mining platform. Neoplasia 6, 1-6

Satake, H., Tamura, K., Furihata, M., Anchi, T., Sakoda, H., Kawada, C., Iiyama, T., Ashida, S., Shuin, T., 2010. The ubiquitin-like molecule interferon-stimulated gene 15 is overexpressed in human prostate cancer. Oncol. Rep. 23, 11-16

Simard, J., Veilleux, R., de Launoit, Y., Haagensen, D.E., Labrie, F., 1991. Stimulation of apolipoprotein D secretion by steroids coincides with inhibition of cell proliferation in human LNCaP prostate cancer cells. Cancer Res. 51, 4336-4341

Sun, G.G., Wang, Y.D., Cui, D.W., Cheng, Y.J., Hu, W.N., 2014. EMP1 regulates caspase-9 and VEGFC expression and suppresses prostate cancer cell proliferation and invasion. Tumour Biol. 35, 3455-3462

Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soerjomataram, I., Jemal, A., Bray, F., 2021. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA. Cancer J. Clin. 71, 209-249

Taylor, B.S., Schultz, N., Hieronymus, H., Gopalan, A., Xiao, Y., Carver, B.S., Arora, V.K., Kaushik, P., Cerami, E., Reva, B., Antipin, Y., Mitsiades, N., Landers, T., Dolgalev, I., Major, J.E., Wilson, M., Socci, N.D., Lash, A.E., Heguy, A., Eastham, J.A., Scher, H.I., Reuter, V.E., Scardino, P.T., Sander, C., Sawyers, C.L., Gerald, W.L., 2010. Integrative genomic profiling of human prostate cancer. Cancer Cell 18, 11-22

Toivanen, R., Shen, M.M., 2017. Prostate organogenesis: tissue induction, hormonal regulation and cell type specification. Development 144, 1382-1398

Tomlins, S.A., Mehra, R., Rhodes, D.R., Cao, X., Wang, L., Dhanasekaran, S.M., Kalyana-Sundaram, S., Wei, J.T., Rubin, M.A., Pienta, K.J., Shah, R.B., Chinnaiyan, A.M., 2007. Integrative molecular concept modeling of prostate cancer progression. Nat. Genet. 39, 41-51

Uehara, H., Takahashi, T., Izumi, K., 2013. Induction of retinol-binding protein 4 and placenta-specific 8 expression in human prostate cancer cells remaining in bone following osteolytic tumor growth inhibition by osteoprotegerin. Int. J. Oncol. 43, 365-374

Urieli-Shoval, S., Cohen, P., Eisenberg, S., Matzner, Y., 1998. Widespread expression of serum amyloid A in histologically normal human tissues. Predominant localization to the epithelium. J. Histochem. Cytochem. 46, 1377-1384

Vainio, P., Gupta, S., Ketola, K., Mirtti, T., Mpindi, J.P., Kohonen, P., Fey, V., Perala, M., Smit, F., Verhaegh, G., Schalken, J., Alanen, K.A., Kallioniemi, O., Iljin, K., 2011. Arachidonic acid pathway members PLA2G7, HPGD, EPHX2, and CYP4F8 identified as putative novel therapeutic targets in prostate cancer. Am. J. Pathol. 178, 525-536

Vancauwenberghe, E., Noyer, L., Derouiche, S., Lemonnier, L., Gosset, P., Sadofsky, L.R., Mariot, P., Warnier, M., Bokhobza, A., Slomianny, C., Mauroy, B., Bonnal, J.L., Dewailly, E., Delcourt, P., Allart, L., Desruelles, E., Prevarskaya, N., Roudbaraki, M., 2017. Activation of mutated TRPA1 ion channel by resveratrol in human prostate cancer associated fibroblasts (CAF). Mol. Carcinog. 56, 1851-1867

Vital, P., Castro, P., Tsang, S., Ittmann, M., 2014. The senescence-associated secretory phenotype promotes benign prostatic hyperplasia. Am. J. Pathol. 184, 721-731

Wang, Y., Hayward, S., Cao, M., Thayer, K., Cunha, G., 2001. Cell differentiation lineage in the prostate. Differentiation 68, 270-279

Wang, Z., Xu, D., Ding, H.F., Kim, J., Zhang, J., Hai, T., Yan, C., 2015. Loss of ATF3 promotes Akt activation and prostate cancer development in a Pten knockout mouse model. Oncogene 34, 4975-4984

Xiao, W., Wang, X., Wang, T., Xing, J., 2019. MiR-223-3p promotes cell proliferation and metastasis by downregulating SLC4A4 in clear cell renal cell carcinoma. Aging (Albany NY) 11, 615-633

Zhang, R., Chen, H.Z., Liu, D.P., 2015. The Four Layers of Aging. Cell Syst. 1, 180-186

Zhu, J.G., Yuan, D.B., Chen, W.H., Han, Z.D., Liang, Y.X., Chen, G., Fu, X., Liang, Y.K., Chen, G.X., Sun, Z.L., Liu, Z.Z., Chen, J.H., Jiang, F.N., Zhong, W.D., 2016. Prognostic value of ZFP36 and SOCS3 expressions in human prostate cancer. Clin. Transl. Oncol. 18, 782-791

Zou, Q., Cui, D., Liang, S., Xia, S., Jing, Y., Han, B., 2016. Aging up-regulates ARA55 in stromal cells, inducing androgen-mediated prostate cancer cell proliferation and migration. J. Mol. Histol. 47, 305-315

Relative Articles

Supplements(0)

Cited By

Proportional views