A potential regulatory loop between Lin28B:miR‑212 in androgen-independent prostate cancer

Borrego-Diaz,Emma; Powers,Benjamin  C.; Azizov,Vugar; Lovell,Scott; Reyes,Ruben; Chapman,Bradley; Tawfik,Ossama; McGregor,Douglas; Diaz,Francisco  J.; Wang,Xinkun; Veldhuizen,Peter   Van

doi:10.3892/ijo.2014.2647

A potential regulatory loop between Lin28B:miR‑212 in androgen-independent prostate cancer

Authors:
- Emma Borrego-Diaz
- Benjamin C. Powers
- Vugar Azizov
- Scott Lovell
- Ruben Reyes
- Bradley Chapman
- Ossama Tawfik
- Douglas McGregor
- Francisco J. Diaz
- Xinkun Wang
- Peter Van Veldhuizen
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Affiliations: Division of Hematology/Oncology, Department of Internal Medicine, University of Kansas Medical Center, Westwood, KS 66205, USA, Protein Structure Laboratory, Del Shankel Structural Biology Center, University of Kansas, Main Campus, Lawrence, KS 66047, USA, University of Kansas Cancer Center, Kansas City, KS 66160, USA, Veterans Administration Medical Center, Kansas City, MO 64128, USA, Genomic Facility, University of Kansas, Main Campus, Lawrence, KS 66047, USA
Published online on: September 9, 2014 https://doi.org/10.3892/ijo.2014.2647
Pages: 2421-2429

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Abstract

Lin28 is a family of RNA binding proteins and microRNA regulators. Two members of this family have been identified: Lin28A and Lin28B, which are encoded by genes localized in different chromosomes but share a high degree of sequence identity. The role of Lin28B in androgen-independent prostate cancer (AIPC) is not well understood. Lin28B is expressed in all grades of prostatic carcinomas and prostate cancer cell lines, but not in normal prostate tissue. In this study we found that Lin28B co-localized in the nucleus and cytoplasm of the DU145 AIPC. The expression of Lin28B protein positively correlated with the expression of the c-Myc protein in the prostate cancer cell lines and silencing of Lin28B also correlated with a lower expression of the c-Myc protein, but not with the downregulation of c-Myc messenger RNA (mRNA) in the DU145 AIPC cells. We hypothesized that Lin28B regulates the expression of c-Myc protein by altering intermediate c-Myc suppressors. Therefore, a microRNA profile of DU145 cells was performed after Lin28B siRNA silencing. Nineteen microRNAs were upregulated and eleven microRNAs were downregulated. The most upregulated microRNAs were miR-212 and miR-2278. Prior reports have found that miR-212 is suppressed in prostate cancer. We then ran TargetScan software to find potential target mRNAs of miR-212 and miR-2278, and it predicted Lin28B mRNA as a potential target of miR-212, but not miR-2278. TargetScan also predicted that c-Myc mRNA is not a potential target of miR-212 or miR-2278. These observations suggest that Lin28B:miR-212 may work as a regulatory loop in androgen-independent prostate cancer. Furthermore, we report a predictive 2-fold symmetric model generated by the superposition of the Lin28A structure onto the I-TASSER model of Lin28B. This structural model of Lin28B suggests that it shows unique microRNA binding characteristics. Thus, if Lin28B were to bind miRNAs in a manner similar to Lin28A, conformational changes would be necessary to prevent steric clashes in the C-terminal and linker regions between the CSD and ZNF domains.

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1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar
2	Crawford ED, Stone NN, Yu EY, et al: Challenges and recommendations for early identification of metastatic disease in prostate cancer. Urology. 83:664–669. 2014. View Article : Google Scholar : PubMed/NCBI
3	Trendel JA: The hurdle of antiandrogen drug resistance: drug design strategies. Expert Opin Drug Discov. 8:1491–1501. 2013. View Article : Google Scholar : PubMed/NCBI
4	Mirnezami AH, Pickard K, Zhang L, Primrose JN and Packham G: MicroRNAs: key players in carcinogenesis and novel therapeutic targets. Eur J Surg Oncol. 35:339–347. 2009. View Article : Google Scholar : PubMed/NCBI
5	Ritchie W, Rasko JE and Flamant S: MicroRNA target prediction and validation. Adv Exp Med Biol. 774:39–53. 2013. View Article : Google Scholar : PubMed/NCBI
6	Lovat F, Valeri N and Croce CM: MicroRNAs in the pathogenesis of cancer. Semin Oncol. 38:724–733. 2011. View Article : Google Scholar : PubMed/NCBI
7	Hafner M, Max KE, Bandaru P, et al: Identification of mRNAs bound and regulated by human LIN28 proteins and molecular requirements for RNA recognition. RNA. 19:613–626. 2013. View Article : Google Scholar : PubMed/NCBI
8	Zhou J, Ng SB and Chng WJ: LIN28/LIN28B: an emerging oncogenic driver in cancer stem cells. Int J Biochem Cell Biol. 45:973–978. 2013. View Article : Google Scholar : PubMed/NCBI
9	Gaytan F, Sangiao-Alvarellos S, Manfredi-Lozano M, et al: Distinct expression patterns predict differential roles of the miRNA-binding proteins, Lin28 and Lin28b, in the mouse testis: studies during postnatal development and in a model of hypogonadotropic hypogonadism. Endocrinology. 154:1321–1336. 2013. View Article : Google Scholar
10	Tummala R, Nadiminty N, Lou W, et al: Lin28 promotes growth of prostate cancer cells and activates the androgen receptor. Am J Pathol. 183:288–295. 2013. View Article : Google Scholar : PubMed/NCBI
11	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001.
12	Roy A, Kucukural A and Zhang Y: I-TASSER: a unified platform for automated protein structure and function prediction. Nat Protoc. 5:725–738. 2010. View Article : Google Scholar : PubMed/NCBI
13	Walter BA, Valera VA, Pinto PA and Merino MJ: Comprehensive microRNA profiling of prostate cancer. J Cancer. 4:350–357. 2013. View Article : Google Scholar
14	Incoronato M, Urso L, Portela A, et al: Epigenetic regulation of miR-212 expression in lung cancer. PLoS One. 6:e277222011. View Article : Google Scholar : PubMed/NCBI
15	Xu B, Wang N, Wang X, et al: MiR-146a suppresses tumor growth and progression by targeting EGFR pathway and in a p-ERK-dependent manner in castration-resistant prostate cancer. Prostate. 72:1171–1178. 2012. View Article : Google Scholar : PubMed/NCBI
16	Jones CI, Zabolotskaya MV, King AJ, et al: Identification of circulating microRNAs as diagnostic biomarkers for use in multiple myeloma. Br J Cancer. 107:1987–1996. 2012. View Article : Google Scholar : PubMed/NCBI
17	Endo Y, Toyama T, Takahashi S, et al: miR-1290 and its potential targets are associated with characteristics of estrogen receptor alpha-positive breast cancer. Endocr Relat Cancer. 20:91–102. 2013. View Article : Google Scholar : PubMed/NCBI
18	Sand M, Skrygan M, Sand D, et al: Comparative microarray analysis of microRNA expression profiles in primary cutaneous malignant melanoma, cutaneous malignant melanoma metastases, and benign melanocytic nevi. Cell Tissue Res. 351:85–98. 2013. View Article : Google Scholar
19	Nurul-Syakima AM, Yoke-Kqueen C, Sabariah AR, Shiran MS, Singh A and Learn-Han L: Differential microRNA expression and identification of putative miRNA targets and pathways in head and neck cancers. Int J Mol Med. 28:327–336. 2011.PubMed/NCBI
20	Wang Z, Zhang H, Zhang P, Li J, Shan Z and Teng W: Upregulation of miR-2861 and miR-451 expression in papillary thyroid carcinoma with lymph node metastasis. Med Oncol. 30:5772013. View Article : Google Scholar : PubMed/NCBI
21	Xu K, Liang X, Cui D, Wu Y, Shi W and Liu J: miR-1915 inhibits Bcl-2 to modulate multidrug resistance by increasing drug-sensitivity in human colorectal carcinoma cells. Mol Carcinog. 52:70–78. 2013. View Article : Google Scholar : PubMed/NCBI
22	Hu H, Li S, Cui X, et al: The overexpression of hypomethylated miR-663 induces chemotherapy resistance in human breast cancer cells by targeting heparin sulfate proteoglycan 2 (HSPG2). J Biol Chem. 288:10973–10985. 2013. View Article : Google Scholar : PubMed/NCBI
23	An J, Pan Y, Yan Z, et al: MiR-23a in amplified 19p13.13 loci targets metallothionein 2A and promotes growth in gastric cancer cells. J Cell Biochem. 114:2160–2169. 2013. View Article : Google Scholar : PubMed/NCBI
24	Li JH, Xiao X, Zhang YN, et al: 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
25	Ferrajoli A, Shanafelt TD, Ivan C, et al: Prognostic value of miR-155 in individuals with monoclonal B-cell lymphocytosis and patients with B chronic lymphocytic leukemia. Blood. 122:1891–1899. 2013. View Article : Google Scholar : PubMed/NCBI
26	Oh JS, Kim JJ, Byun JY and Kim IA: Lin28-let7 modulates radiosensitivity of human cancer cells with activation of K-Ras. Int J Radiat Oncol Biol Phys. 76:5–8. 2010. View Article : Google Scholar : PubMed/NCBI
27	Cui MH, Hou XL, Lei XY, et al: Upregulation of microRNA 181c expression in gastric cancer tissues and plasma. Asian Pac J Cancer Prev. 14:3063–3066. 2013. View Article : Google Scholar : PubMed/NCBI
28	Jiang L, Lin C, Song L, et al: MicroRNA-30e^* promotes human glioma cell invasiveness in an orthotopic xenotransplantation model by disrupting the NF-κB/IκBα negative feedback loop. J Clin Invest. 122:33–47. 2012.
29	Kashat M, Azzouz L, Sarkar SH, Kong D, Li Y and Sarkar FH: Inactivation of AR and Notch-1 signaling by miR-34a attenuates prostate cancer aggressiveness. Am J Transl Res. 4:432–442. 2012.PubMed/NCBI
30	Schaefer A, Jung M, Mollenkopf HJ, et al: Diagnostic and prognostic implications of microRNA profiling in prostate carcinoma. Int J Cancer. 126:1166–1176. 2010.PubMed/NCBI
31	Man YG, Fu SW, Liu AJ, et al: Aberrant expression of chromogranin A, miR-146a, and miR-146b-5p in prostate structures with focally disrupted basal cell layers: an early sign of invasion and hormone-refractory cancer? Cancer Genomics Proteomics. 8:235–244. 2011.PubMed/NCBI
32	Bray I, Tivnan A, Bryan K, et al: MicroRNA-542-5p as a novel tumor suppressor in neuroblastoma. Cancer Lett. 303:56–64. 2011. View Article : Google Scholar : PubMed/NCBI
33	Yang L, Li Y, Cheng M, et al: A functional polymorphism at microRNA-629-binding site in the 3′-untranslated region of NBS1 gene confers an increased risk of lung cancer in Southern and Eastern Chinese population. Carcinogenesis. 33:338–347. 2012.PubMed/NCBI
34	Ali PS, Ghoshdastider U, Hoffmann J, Brutschy B and Filipek S: Recognition of the let-7g miRNA precursor by human Lin28B. FEBS Lett. 586:3986–3990. 2012. View Article : Google Scholar : PubMed/NCBI
35	Nam Y, Chen C, Gregory RI, Chou JJ and Sliz P: Molecular basis for interaction of let-7 microRNAs with Lin28. Cell. 147:1080–1091. 2011. View Article : Google Scholar : PubMed/NCBI
36	Nadiminty N, Tummala R, Lou W, et al: MicroRNA let-7c is downregulated in prostate cancer and suppresses prostate cancer growth. PLoS One. 7:e328322012. View Article : Google Scholar : PubMed/NCBI
37	Vencio EF, Nelson AM, Cavanaugh C, et al: Reprogramming of prostate cancer-associated stromal cells to embryonic stem-like. Prostate. 72:1453–1463. 2012. View Article : Google Scholar : PubMed/NCBI
38	Kong D, Banerjee S, Ahmad A, et al: Epithelial to mesenchymal transition is mechanistically linked with stem cell signatures in prostate cancer cells. PLoS One. 5:e124452010. View Article : Google Scholar : PubMed/NCBI