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Treating metastatic prostate cancer with microRNA-145

Treating metastatic prostate cancer with microRNA-145 Prostate cancer (PCa) is an incurable disease at the metastatic stage. Although there are different options for treatment, the results are limited. MicroRNAs (miRNAs) are a group of small, noncoding, regulatory RNAs with important roles in regulating gene expression. miR-145 is reported to be a key tumor suppressor miRNA (tsmiR) that controls important oncogenes, such as MYC and RAS. In this study, in vitro studies were performed to show the control of MYC and RAS by miR-145. Flow cytometry was used to analyze cell proliferation and apoptosis. The efficacy of miR-145 in treating metastatic PCa was tested in nude mice using a model of bone metastasis promoted by intraventricular injection of PC-3MLuc-C6 cells. Tumor growth was evaluated by an in vivo bioluminescence system. After the full establishment of metastases on day 21, six animals were treated with three intravenous doses of miR-145 (on days 21, 24 and 27), and six were injected with scramble miRNA as controls. Compared to the controls, tumor growth was significantly reduced in animals receiving miR-145, most importantly on day 7 after the third and last dose of miRNA. After discontinuing the treatment, tumor growth resumed, becoming similar to the group of non-treated animals. A decrease in MYC and RAS expression was observed in all cell lines after treatment with miR-145, although statistical significance was achieved only in experiments with LNCaP and PC3 cell lines, with a decrease in 56% (p = 0.012) and 31% (p = 0.013) of RAS expression, respectively. Our results suggest that miR-145 is a potential molecule to be tested for treatment of metastatic, castration-resistant PCa. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Apoptosis Springer Journals

Treating metastatic prostate cancer with microRNA-145

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Publisher
Springer Journals
Copyright
Copyright © 2018 by Springer Science+Business Media, LLC, part of Springer Nature
Subject
Biomedicine; Cancer Research; Cell Biology; Oncology; Biochemistry, general; Virology
ISSN
1360-8185
eISSN
1573-675X
DOI
10.1007/s10495-018-1461-z
Publisher site
See Article on Publisher Site

Abstract

Prostate cancer (PCa) is an incurable disease at the metastatic stage. Although there are different options for treatment, the results are limited. MicroRNAs (miRNAs) are a group of small, noncoding, regulatory RNAs with important roles in regulating gene expression. miR-145 is reported to be a key tumor suppressor miRNA (tsmiR) that controls important oncogenes, such as MYC and RAS. In this study, in vitro studies were performed to show the control of MYC and RAS by miR-145. Flow cytometry was used to analyze cell proliferation and apoptosis. The efficacy of miR-145 in treating metastatic PCa was tested in nude mice using a model of bone metastasis promoted by intraventricular injection of PC-3MLuc-C6 cells. Tumor growth was evaluated by an in vivo bioluminescence system. After the full establishment of metastases on day 21, six animals were treated with three intravenous doses of miR-145 (on days 21, 24 and 27), and six were injected with scramble miRNA as controls. Compared to the controls, tumor growth was significantly reduced in animals receiving miR-145, most importantly on day 7 after the third and last dose of miRNA. After discontinuing the treatment, tumor growth resumed, becoming similar to the group of non-treated animals. A decrease in MYC and RAS expression was observed in all cell lines after treatment with miR-145, although statistical significance was achieved only in experiments with LNCaP and PC3 cell lines, with a decrease in 56% (p = 0.012) and 31% (p = 0.013) of RAS expression, respectively. Our results suggest that miR-145 is a potential molecule to be tested for treatment of metastatic, castration-resistant PCa.

Journal

Apoptosis – Springer Journals

Published: Jun 1, 2018

References

  • An open-label, phase 2 trial of bicalutamide dose escalation from 50 mg to 150 mg in men with CAB and castration resistance. A Canadian Urology Research Consortium Study
    Klotz, L; Drachenberg, D; Singal, R; Aprikian, A; Fradet, Y; Kebabdjian, M
  • Enzalutamide versus bicalutamide in castration-resistant prostate cancer: the STRIVE trial
    Penson, DF; Armstrong, AJ; Concepcion, R; Agarwal, N; Olsson, C; Karsh, L
  • Biogenesis of small RNAs in animals
    Kim, VN; Han, J; Siomi, MC
  • The role of microRNAs in prostate cancer progression
    Lo, UG; Yang, D; Hsieh, JT
  • MicroRNAs and cancer: a long story for short RNAs
    Drusco, A; Croce, CM
  • RNAi therapeutics and applications of microRNAs in cancer treatment
    Uchino, K; Ochiya, T; Takeshita, F
  • Molecular pathways: microRNAs as cancer therapeutics
    Melo, SA; Kalluri, R
  • The inhibition of the highly expressed miR-221 and miR-222 impairs the growth of prostate carcinoma xenografts in mice
    Mercatelli, N; Coppola, V; Bonci, D; Miele, F; Costantini, A; Guadagnoli, M
  • Efficient delivery of small interfering RNA to bone-metastatic tumors by using atelocollagen in vivo
    Takeshita, F; Minakuchi, Y; Nagahara, S; Honma, K; Sasaki, H; Hirai, K
  • Systemic delivery of synthetic microRNA-16 inhibits the growth of metastatic prostate tumors via downregulation of multiple cell-cycle genes
    Takeshita, F; Patrawala, L; Osaki, M; Takahashi, RU; Yamamoto, Y; Kosaka, N
  • Change in expression of miR-let7c, miR-100, and miR-218 from high grade localized prostate cancer to metastasis
    Leite, KR; Sousa-Canavez, JM; Reis, ST; Tomiyama, AH; Camara-Lopes, LH; Sanudo, A
  • miRNAs in human cancer
    Farazi, TA; Spitzer, JI; Morozov, P; Tuschl, T
  • Widespread deregulation of microRNA expression in human prostate cancer
    Ozen, M; Creighton, CJ; Ozdemir, M; Ittmann, M
  • Diagnostic, prognostic and therapeutic implications of microRNAs in urologic tumors
    Schaefer, A; Stephan, C; Busch, J; Yousef, GM; Jung, K
  • MicroRNA profiles of prostate carcinoma detected by multiplatform microRNA screening
    Wach, S; Nolte, E; Szczyrba, J; Stohr, R; Hartmann, A; Orntoft, T
  • The loss of the tumour-suppressor miR-145 results in the shorter disease-free survival of prostate cancer patients
    Avgeris, M; Stravodimos, K; Fragoulis, EG; Scorilas, A
  • The proto-oncogene ERG is a target of microRNA miR-145 in prostate cancer
    Hart, M; Wach, S; Nolte, E; Szczyrba, J; Menon, R; Taubert, H
  • MicroRNA in prostate cancer: practical aspects
    Patil, PA; Magi-Galluzzi, C
  • Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis
    Bissler, JJ; McCormack, FX; Young, LR; Elwing, JM; Chuck, G; Leonard, JM
  • MicroRNA expression profiles in the progression of prostate cancer–from high-grade prostate intraepithelial neoplasia to metastasis
    Leite, KR; Tomiyama, A; Reis, ST; Sousa-Canavez, JM; Sanudo, A; Camara-Lopes, LH
  • Controlling RECK miR21 promotes tumor cell invasion and is related to biochemical recurrence in prostate cancer
    Leite, KR; Reis, ST; Viana, N; Morais, DR; Moura, CM; Silva, IA
  • The impact of miRNA target sites in coding sequences and in 3′UTRs
    Fang, Z; Rajewsky, N
  • The role of rechallenge with targeted therapies in metastatic renal-cell carcinoma
    Oudard, S; Vano, Y
  • Cyclooxygenase-2 inhibitor suppresses tumour progression of prostate cancer bone metastases in nude mice
    Garcia, M; Velez, R; Romagosa, C; Majem, B; Pedrola, N; Olivan, M
  • Targeting mutant BRAF in relapsed or refractory hairy-cell leukemia
    Tiacci, E; Park, JH; Carolis, L; Chung, SS; Broccoli, A; Scott, S
  • A river model to map convergent cancer evolution and guide therapy in RCC
    Wei, EY; Hsieh, JJ