Prostat kanseri moleküler mekanizmasında kodlanmayan RNA’ların rolü

Kodlanmayan RNA’lar (ncRNA), bir açık okuma çerçevesi bulunmayan ve proteine çevrilemeyen işlevsel RNA transkriptleridir. NcRNA’lar transkripsiyon ve transkripsiyon sonrası işlemlerde düzenleyici rollere ve halen açıklanmaya devam eden çok sayıda hücresel fonksiyona sahiptir. NcRNA’lardan en iyi bilinenleri mikro RNA’lar (miRNA), hedefledikleri genlerin ya translasyonel baskılanmasına ya da mRNA yıkımına yol açarak gen ifadesini düzenleyen küçük (~22 nt) RNA molekülleridir. Uzun kodlanmayan RNA’lar (lncRNA), uzunluğu 200 nükleotidden daha büyük olan ve birçok alt sınıfı bulunan heterojen RNA’lardır. Bu RNA molekülleri kendilerine özgül ikincil ve üçüncül yapıları gereği DNA veya proteinler ile etkileşime girerek kromatin yeniden şekillenmesi, histon modifikasyonu, gen ifadesinin transkripsiyonel ve translasyonel düzenlenmesi gibi önemli işlevler üstlenirler. Hem miRNA’lar hem de lncRNA’lar prostat kanseri dâhil birçok kanser çeşidinde düzensiz ifade edilmektedirler. Bu derleme, miRNA, lncRNA ve diğer ncRNA’ların prostat kanserinin moleküler biyolojisinde önemini açıklayarak prostat kanserinin ayırıcı tanısında ve hedeflenebilir tedavisinde kullanılabilirliğini vurgulamaktadır.

Anahtar Kelimeler:

lncRNA, miRNA, ncRNA, prostat kanseri

The Role of Non-Coding RNAs in Molecular Mechanism of Prostate Cancer

Non-coding RNAs (ncRNAs) are functional RNA transcripts, which have not an open-reading frame and cannot be translated into protein. ncRNAs have mediator roles in the transcription and the post-transcription processes and have numerous cellular functions which still continue to be explored. The best known of ncRNAs, microRNAs (miRNAs) are small RNA molecules (~22 nt) which regulate the expressions of the targeted genes by leading to either of the transcriptional repression or mRNA degradation. Longer than 200 nucleotides, long non-coding RNAs (lncRNAs) are heterogenic RNAs which have many subclasses. These RNA molecules play a part in chromatin remodeling, histone modification, and transcriptional and translational gene expression regulations by interacting with DNA or proteins by their secondary and tertiary structural nature. miRNAs and lncRNAs are irregularly expressed in many types of cancer including prostate cancer. The present review explains the importance of miRNA, lncRNA, and other ncRNAs in the molecular biology of prostate cancer and emphasizes their employability in the diagnosis and the targetable treatments.

Keywords:

lncRNA, miRNA, ncRNA, prostate cancer,

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Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA: a cancer journal for clinicians. 2019;69(1):7-34.
Potosky AL, Miller BA, Albertsen PC., Kramer BS. The role of increasing detection in the rising incidence of prostate cancer. Jama. 1995;273(7):548-552.
Fedewa SA, Ward EM, Brawley O, Jemal A. Recent patterns of prostate-specific antigen testing for prostate cancer screening in the United States. JAMA Intern Med. 2017;177(7):1040-1042.
Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA. 2006;103(7):2257-2261.
Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan E, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 2008;105(30):10513-10518.
Brase JC, Johannes M, Schlomm T, Fälth M, Haese A, Steuber T, et al. Circulating miRNAs are correlated with tumor progression in prostate cancer. Int J Cancer. 2011;128(3):608-616.
Lodes MJ, Caraballo M, Suciu D, Munro S, Kumar A, Anderson B. Detection of cancer with serum miRNAs on an oligonucleotide microarray. PloS one. 2009;4(7):e6229.
Szczyrba J, Löprich E, Wach S, Jung V, Unteregger G, Barth S et al. The microRNA profile of prostate carcinoma obtained by deep sequencing. Mol Cancer Res. 2010;8(4):529-538.
Schaefer A, Jung M, Mollenkopf HJ, Wagner I, Stephan C, Jentzmik F, et al. Diagnostic and prognostic implications of microRNA profiling in prostate carcinoma. Int J Cancer. 2010;126(5):1166-1176.
Liu DF, Wu JT, Wang JM, Liu QZ, Gao ZL, Liu YX. MicroRNA expression profile analysis reveals diagnostic biomarker for human prostate cancer. Asian Pac J Cancer Prev. 2012;13(7):3313-3317.
Kachakova D, Mitkova A, Popov E, Popov I, Vlahova A, Dikov T. et al. Combinations of serum prostate-specific antigen and plasma expression levels of let-7c, miR-30c, miR-141, and miR-375 as potential better diagnostic biomarkers for prostate cancer. DNA Cell Biol. 2015;34(3):189-200.
Bryant RJ, Pawlowski T, Catto JWF, Marsden G, Vessella RL, Rhees B, et al. Changes in circulating microRNA levels associated with prostate cancer. Br J Cancer. 2012;106(4):768-774.
Pickl JM, Tichy D, Kuryshev VY, Tolstov Y, Falkenstein M, Schuler J, et al. Ago-RIP-Seq identifies Polycomb repressive complex I member CBX7 as a major target of miR-375 in prostate cancer progression. Oncotarget. 2016;7(37):59589-59603.
Selth LA, Das R, Townley SL, Coutinho I, Hanson AR, Centenera MM, et al. A ZEB1-miR-375-YAP1 pathway regulates epithelial plasticity in prostate cancer. Oncogene. 2017;36(1):24-34.
Szczyrba J, Nolte E, Wach S, Kremmer E, Stohr R, Hartmann A, et al. Downregulation of Sec23A protein by miRNA-375 in prostate carcinoma. Mol Cancer Res. 2011;9(6):791-800.
Wang Y, Lieberman R, Pan J, Zhang Q, Du M, Zhang P, et al. miR-375 induces docetaxel resistance in prostate cancer by targeting SEC23A and YAP1. Mol Cancer. 2016;15(1):70.
Dong Q, Meng P, Wang T, Qin W, Qin W, Wang F, et al. MicroRNA let-7a inhibits proliferation of human prostate cancer cells in vitro and in vivo by targeting E2F2 and CCND2. PLoS One. 2010;5(4):e10147.
Tang G., Du R., Tang Z. Kuang Y. MiRNALet-7a mediates prostate cancer PC-3 cell invasion, migration by inducing epithelial-mesenchymal transition through CCR7/MAPK pathway. J Cell Biochem. 2018;119(4):3725-3731.
Zhao B, Lu YL, Yang Y, Hu LB, Bai Y, Li RQ, et al. Overexpression of lncRNA ANRIL promoted the proliferation and migration of prostate cancer cells via regulating let-7a/TGF-beta1/ Smad signaling pathway. Cancer Biomark. 2018;21(3):613-620.
Chakravarthi B, Chandrashekar DS, Agarwal S, Balasubramanya SAH, Pathi SS, Goswami MT, et al. miR-34a Regulates Expression of the Stathmin-1 Oncoprotein and Prostate Cancer Progression. Mol Cancer Res. 2018;16(7):1125-1137.
Liang J, Li Y, Daniels G, Sfanos K, De Marzo A, Wei J, et al. LEF1 Targeting EMT in Prostate Cancer Invasion Is Regulated by miR-34a. Mol Cancer Res. 2015;13(4):681-688.
Liu X, Luo X, Wu Y, Xia D, Chen W, Fang Z, et al. MicroRNA-34a Attenuates Paclitaxel Resistance in Prostate Cancer Cells via Direct Suppression of JAG1/Notch1 Axis. Cell Physiol Biochem. 2018;50(1):261-276.
Zhang G, Tian X, Li Y, Wang Z, Li X, Zhu C. miR-27b and miR-34a enhance docetaxel sensitivity of prostate cancer cells through inhibiting epithelial-to-mesenchymal transition by targeting ZEB1. Biomed Pharmacother. 2018;97:736-744.
Huang S, Wa Q, Pan J, Peng X, Ren D, Huang Y, et al. Downregulation of miR-141-3p promotes bone metastasis via activating NF-kappaB signaling in prostate cancer. J Exp Clin Cancer Res. 2017;36(1):173.
Khorasani M, Teimoori-Toolabi L, Farivar TN, Asgari M, Abolhasani M, Shahrokh H, et al. Aberrant expression of miR-141 and nuclear receptor small heterodimer partner in clinical samples of prostate cancer. Cancer Biomark. 2018;22(1):19-28.
Li JZ, Li J, Wang HQ, Li X, Wen B, Wang YJ. MiR-141-3p promotes prostate cancer cell proliferation through inhibiting kruppel-like factor-9 expression. Biochem Biophys Res Commun. 2017;482(4):1381-1386.
Li Z, Ma YY, Wang J, Zeng XF, Li R, Kang W, et al. Exosomal microRNA-141 is upregulated in the serum of prostate cancer patients. Onco Targets Ther. 2016;9:139-148.
Liu C, Liu R, Zhang D, Deng Q, Liu B, Chao HP, et al. MicroRNA-141 suppresses prostate cancer stem cells and metastasis by targeting a cohort of pro-metastasis genes. Nat Commun. 2017;8:14270.
Zhao H, Lai X, Zhang W, Zhu H, Zhang S, Wu W, et al. MiR-30a-5p frequently downregulated in prostate cancer inhibits cell proliferation via targeting PCLAF. Artif Cells Nanomed Biotechnol. 2019;47(1):278-289.
Wu G, Sun Y, Xiang Z, Wang K, Liu B, Xiao G, et al. Preclinical study using circular RNA 17 and micro RNA 181c-5p to suppress the enzalutamide-resistant prostate cancer progression. Cell Death Dis. 2019;10(2):37.
Xu B, Lu X, Zhao Y, Liu C, Huang X, Chen S, et al. MicroRNA-135a induces prostate cancer cell apoptosis via inhibition of STAT6. Oncol Lett. 2019;17(2):1889-1895.
Deng J, Ma M, Jiang W, Zhang H. Cui S. miR-493 Promotes Prostate Cancer Cells Proliferation by Targeting PHLPP2 and Activating Akt Signaling Pathway. Clin Lab. 2019;65(3).
Peng P, Chen T, Wang Q, Zhang Y, Zheng F, Huang S. et al. Decreased miR-218-5p Levels as a Serum Biomarker in Bone Metastasis of Prostate Cancer. Oncol Res Treat. 2019;42(4):165-185.
Sang Z, Jiang X, Guo L, Yin G. MicroRNA9 suppresses human prostate cancer cell viability, invasion and migration via modulation of mitogenactivated protein kinase kinase kinase 3 expression. Mol Med Rep. 2019;19(5):4407-4418.
Yin W, Chen J, Wang G, Zhang D. MicroRNA106b functions as an oncogene and regulates tumor viability and metastasis by targeting LARP4B in prostate cancer. Mol Med Rep. 2019;20(2):951-958.
Guan Y, Guan X, An H, Baihetiya A, Wang W, Shao W, et al. Epigenetic silencing of miR-137 induces resistance to bicalutamide by targeting TRIM24 in prostate cancer cells. Am J Transl Res. 2019;11(5):3226-3237.
Feng Q, He P, Wang Y. MicroRNA-223-3p regulates cell chemo-sensitivity by targeting FOXO3 in prostatic cancer. Gene. 2018;658(152-158.
Hao P, Kang B, Yao G, Hao W, Ma F. MicroRNA-211 suppresses prostate cancer proliferation by targeting SPARC. Oncol Lett. 2018;15(4):4323-4329.
Wang Y, Xu H, Si L, Li Q, Zhu X, Yu T. et al. MiR-206 inhibits proliferation and migration of prostate cancer cells by targeting CXCL11. Prostate. 2018;78(7):479-490.
Li J, Fu F, Wan X, Huang S, Wu D, Li Y. Up-regulated miR-29c inhibits cell proliferation and glycolysis by inhibiting SLC2A3 expression in prostate cancer. Gene. 2018;665:26-34.
Sun Q, Weng D, Li K, Li S, Bai X, Fang C. et al. MicroRNA-139-5P inhibits human prostate cancer cell proliferation by targeting Notch1. Oncol Lett. 2018;16(1):793-800.
Ostadrahimi S, Fayaz S, Parvizhamidi M, Abedi-Valugerdi M, Hassan M, Kadivar M. et al. Downregulation of miR-1266-5P, miR-185-5P and miR-30c-2 in prostatic cancer tissue and cell lines. Oncol Lett. 2018;15(5):8157-8164.
Zhang Y, Zhang D, Lv J, Wang S, Zhang Q. miR-410-3p promotes prostate cancer progression via regulating PTEN/AKT/mTOR signaling pathway. Biochem Biophys Res Commun. 2018;503(4):2459-2465.
Fang Y, Qiu J, Jiang ZB, Xu SR, Zhou ZH, He RL. Increased serum levels of miR-214 in patients with PCa with bone metastasis may serve as a potential biomarker by targeting PTEN. Oncol Lett. 2019;17(1):398-405.
Lu J, Mu X, Yin Q, Hu K. miR-106a contributes to prostate carcinoma progression through PTEN. Oncol Lett. 2019;17(1):1327-1332.
Zhang M, Li H, Zhang Y, Li H. Oncogenic miR-744 promotes prostate cancer growth through direct targeting of LKB1. Oncol Lett. 2019;17(2):2257-2265.
Fan H, Zhang YS. miR-490-3p modulates the progression of prostate cancer through regulating histone deacetylase 2. Eur Rev Med Pharmacol Sci. 2019;23(2):539-546.
Zhang X, Pan Y, Fu H, Zhang J. microRNA-205 and microRNA-338-3p Reduces Cell Apoptosis in Prostate Carcinoma Tissue and LNCaP Prostate Carcinoma Cells by Directly Targeting the B-Cell Lymphoma 2 (Bcl-2) Gene. Med Sci Monit. 2019;25:1122-1132.
Barros-Silva D, Costa-Pinheiro P, Duarte H, Sousa EJ, Evangelista AF, Graça I, et al. MicroRNA-27a-5p regulation by promoter methylation and MYC signaling in prostate carcinogenesis. Cell death & disease. 2018;9(2):167.
Ozen M, Creighton CJ, Ozdemir M, Ittmann M. Widespread deregulation of microRNA expression in human prostate cancer. Oncogene. 2008;27(12):1788.
Nam RK, Amemiya Y, Benatar T, Wallis CJ, Stojcic-Bendavid J, Bacopulos S. et al. Identification and Validation of a Five MicroRNA Signature Predictive of Prostate Cancer Recurrence and Metastasis: A Cohort Study. J Cancer. 2015;6(11):1160-1171.
Casanova-Salas I, Rubio-Briones J, Calatrava A, Mancarella C, Masia E, Casanova J, et al. Identification of miR-187 and miR-182 as biomarkers of early diagnosis and prognosis in patients with prostate cancer treated with radical prostatectomy. J Urol. 2014;192(1):252-259.
Gebert LF, Rebhan MA, Crivelli SE, Denzler R, Stoffel M, Hall J. Miravirsen (SPC3649) can inhibit the biogenesis of miR-122. Nucleic Acids Res. 2014;42(1):609-621.
Hydbring P, Badalian-Very G. Clinical applications of microRNAs. F1000Research. 2013;2:136-142.
Qu Y, Huang X, Li Z, Liu J, Wu J, Chen D. et al. miR-199a-3p inhibits aurora kinase A and attenuates prostate cancer growth: new avenue for prostate cancer treatment. Am J Pathol. 2014;184(5):1541-1549.
Gonzales JC, Fink LM, Goodman OB, JSymanowski JT, Vogelzang NJ, Ward DC. Comparison of circulating MicroRNA 141 to circulating tumor cells, lactate dehydrogenase, and prostate-specific antigen for determining treatment response in patients with metastatic prostate cancer. Clin Genitourin Cancer. 2011;9(1):39-45.
Mercatelli N, Coppola V, Bonci D, Miele F, Costantini A, Guadagnoli M, et al. The inhibition of the highly expressed miR-221 and miR-222 impairs the growth of prostate carcinoma xenografts in mice. PloS one. 2008;3(12):e4029.
Williams LV, Veliceasa D, Vinokour E, Volpert OV. miR-200b inhibits prostate cancer EMT, growth and metastasis. PLoS One. 2013;8(12):e83991.
Kojima K, Fujita Y, Nozawa Y, Deguchi T, Ito M. MiR-34a attenuates paclitaxel-resistance of hormone-refractory prostate cancer PC3 cells through direct and indirect mechanisms. Prostate. 2010;70(14):1501-1512.
Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H, et al. The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res. 2012;22(9):1775-1789.
Consortium ENCODE Project. The ENCODE (ENCyclopedia of DNA elements) project. Science. 2004;306(5696):636-640.
Bu D, Yu K, Sun S, Xie C, Skogerbø G, Miao R, et al. NONCODE v3. 0: integrative annotation of long noncoding RNAs. Nucleic acids research. 2011;40(1):210-215.
Kawai J, Shinagawa A, Shibata K, Yoshino M, Itoh M, Ishii Y, et al. Functional annotation of a full-length mouse cDNA collection. Nature. 2001;409(6821):685.
Bussemakers MJ, Van Bokhoven A, Verhaegh GW, Smit FP, Karthaus HF, Schalken JA, et al. DD3:: A new prostate-specific gene, highly overexpressed in prostate cancer. Cancer research. 1999;59(23):5975-5979.
Srikantan V, Zou Z, Petrovics G, Xu L, Augustus M, Davis L, et al. PCGEM1, a prostate-specific gene, is overexpressed in prostate cancer. Proc Natl Acad Sci USA. 2000;97(22):12216-12221.
Chung S, Nakagawa H, Uemura M, Piao L, Ashikawa K, Hosono N, et al. Association of a novel long non‐coding RNA in 8q24 with prostate cancer susceptibility. Cancer Sci. 2011;102(1):245-252.
Prensner JR, Iyer MK, Balbin OA, Dhanasekaran SM, Cao Q, Brenner JC, et al. Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression. Nat Biotechnol. 2011;29(8):742.
Crea F, Watahiki A, Quagliata L, Xue H, Pikor L, Parolia A, et al. Identification of a long non-coding RNA as a novel biomarker and potential therapeutic target for metastatic prostate cancer. Oncotarget. 2014;5(3):764-774
Shukla S, Zhang X, Niknafs YS, Xiao L, Mehra R, Cieslik M, et al. Identification and Validation of PCAT14 as Prognostic Biomarker in Prostate Cancer. Neoplasia. 2016;18(8):489-499.
Cui Z, Ren S, Lu J, Wang F, Xu W, Sun Y, et al. The prostate cancer-up-regulated long noncoding RNA PlncRNA-1 modulates apoptosis and proliferation through reciprocal regulation of androgen receptor. Urol Oncol. 2013;31(7):1117-23
Zhang Y, Pitchiaya S, Cieślik M, Niknafs YS, Tien JCY, Hosono Y, et al. Analysis of the androgen receptor–regulated lncRNA landscape identifies a role for ARLNC1 in prostate cancer progression. Nat Genet. 2018;50(6):814.
Das R, Gregory PA, Fernandes RC, Denis I, Wang Q, Townley SL, et al. MicroRNA-194 promotes prostate cancer metastasis by inhibiting SOCS2. Cancer Res. 2017;77(4):1021-1034.
Takayama K, Horie‐Inoue K, Katayama S, Suzuki T, Tsutsumi S, Ikeda K, et al. Androgen‐responsive long noncoding RNA CTBP1‐AS promotes prostate cancer. EMBO J. 2013;32(12):1665-1680.
Gao P, Xia JH, Sipeky C, Dong XM, Zhang Q, Yang Y, et al. Biology and Clinical Implications of the 19q13 Aggressive Prostate Cancer Susceptibility Locus. Cell. 2018;174(3):576-589.e518.
Malik R, Patel L, Prensner JR, Shi Y, Iyer MK, Subramaniyan S, et al. The lncRNA PCAT29 inhibits oncogenic phenotypes in prostate cancer. Mol Cancer Res. 2014;12(8):1081-1087.
Pickard MR, Mourtada-Maarabouni M, Williams GT. Long non-coding RNA GAS5 regulates apoptosis in prostate cancer cell lines. Biochim Biophys Acta. 2013;1832(10):1613-1623.
Zhu M, Chen Q, Liu X, Sun Q, Zhao X, Deng R, et al. lnc RNA H19/miR‐675 axis represses prostate cancer metastasis by targeting TGFBI. FEBS J. 2014;281(16):3766-3775.
Ren S, Liu Y, Xu W, Sun Y, Lu J, Wang F, et al. Long noncoding RNA MALAT-1 is a new potential therapeutic target for castration resistant prostate cancer. J Urol. 2013;190(6):2278-2287.
Misawa A, Takayama K, Fujimura T, Homma Y, Suzuki Y, Inoue S. Androgen‐induced lncRNA POTEF‐AS1 regulates apoptosis‐related pathway to facilitate cell survival in prostate cancer cells. Cancer Sci. 2017;108(3):373-379.
Hessels D, Schalken JA. The use of PCA3 in the diagnosis of prostate cancer. Nat Rev Urol. 2009;6(5):255-261.
Salameh A, Lee AK, Cardo-Vila M, Nunes DN, Efstathiou E, Staquicini FI, et al. PRUNE2 is a human prostate cancer suppressor regulated by the intronic long noncoding RNA PCA3. Proc Natl Acad Sci USA. 2015;112(27):8403-8408.
Petrovics G, Zhang W, Makarem M, Street JP, Connelly R, Sun L, et al. Elevated expression of PCGEM1, a prostate-specific gene with cell growth-promoting function, is associated with high-risk prostate cancer patients. Oncogene. 2004;23(2):605.
Misawa A, Takayama K, Urano T, Inoue S. Androgen-induced long noncoding RNA (lncRNA) SOCS2-AS1 promotes cell growth and inhibits apoptosis in prostate cancer cells. J Biol Chem. 2016;291(34):17861-17880.
Cheng J, Guo JM, Xiao BX, Miao Y, Jiang Z, Zhou H, et al. piRNA, the new non-coding RNA, is aberrantly expressed in human cancer cells. Clin Chim Acta. 2011;412(17-18):1621-1625.
Watanabe T, Tomizawa S, Mitsuya K, Totoki Y, Yamamoto Y, Kuramochi-Miyagawa S, et al. Role for piRNAs and noncoding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus. Science. 2011;332(6031):848-852.
Öner Ç, Coşan DT, Çolak E. Estrogen and androgen hormone levels modulate the expression of PIWI interacting RNA in prostate and breast cancer. PloS one. 2016;11(7):e0159044.
Han R, Zhang L, Gan W, Fu K, Jiang K, Ding J, et al. piRNA‐DQ722010 contributes to prostate hyperplasia of the male offspring mice after the maternal exposed to microcystin‐leucine arginine. Prostate. 2019;79(7):798-812.
Lujambio A, Portela A, Liz J, Melo SA, Rossi S, Spizzo R, et al. CpG island hypermethylation-associated silencing of non-coding RNAs transcribed from ultraconserved regions in human cancer. Oncogene. 2010;29(48):6390-6401.
Sekino Y, Sakamoto N, Goto K, Honma R, Shigematsu Y, Sentani K, et al. Transcribed ultraconserved region Uc.63+ promotes resistance to docetaxel through regulation of androgen receptor signaling in prostate cancer. Oncotarget. 2017;8(55):94259-94270.
Greene J, Baird AM, Casey O, Brady L, Blackshields G, Lim M, et al. Circular RNAs are differentially expressed in prostate cancer and are potentially associated with resistance to enzalutamide. Sci Rep. 2019;9(1):10739.
Kong Z, Wan X, Zhang Y, Zhang P, Zhang Y, Zhang X, et al. Androgen-responsive circular RNA circSMARCA5 is up-regulated and promotes cell proliferation in prostate cancer. Biochem Biophys Res Commun. 2017;493(3):1217-1223.
Huang C, Deng H, Wang Y, Jiang H, Xu R, Zhu X, et al. Circular RNA circABCC4 as the ceRNA of miR‐1182 facilitates prostate cancer progression by promoting FOXP4 expression. J Cell Mol Med. 2019;23(9):6112-6119.