TY - JOUR
T1 - Modulation in the microRNA repertoire is responsible for the stage-specific effects of Akt suppression on murine neuroendocrine prostate cancer
AU - Alwhaibi, Abdulrahman
AU - Gao, Fei
AU - Artham, Sandeep
AU - Hsia, Bernard M.
AU - Mondal, Ashis
AU - Kolhe, Ravindra
AU - Somanath, Payaningal R.
N1 - Funding Information:
This work was supported by the National Institutes of Health grants ( R01HL103952 and UL1TR002378 ). Payaningal R. Somanath was supported by the Wilson Pharmacy Foundation and Translational Research Initiative Grant . Abdulrahman Alwhaibi was supported by a fellowship provided by the King Saud University .
Publisher Copyright:
© 2018
PY - 2018/9
Y1 - 2018/9
N2 - Recent studies indicate a stage-specific, differential role for the oncogene Akt on various cancers. In prostate cancer (PCa), suppression of Akt activity in the advanced stages promoted transforming growth factor-β (TGFβ) pathway-mediated epithelial-to-mesenchymal transition (EMT) and metastasis to the lungs. In the current study, we performed Affymetrix analysis to compare the expression profile of microRNAs in the mouse prostate tissues collected at the prostatic inter-epithelial neoplasia (PIN) stage from Transgenic adenocarcinoma of the mouse (TRAMP)/Akt1+/+ versus TRAMP/Akt1–/– mice, and at the advanced stage from TRAMP/Akt1+/+ mice treated with triciribine (Akt inhibitor) versus DMSO-treated control. Our analysis demonstrates that in the early stage, Akt1 in the TRAMP prostate tumors express a set of miRNAs responsible for regulating cancer cell survival, proliferation, and tumor growth, whereas, in the advanced stages, a different set of miRNAs that promote EMT and cancer metastasis is expressed. Our study has identified novel Akt-regulated signature microRNAs in the early and advanced PCa and demonstrates their differential effects on PCa growth and metastasis.
AB - Recent studies indicate a stage-specific, differential role for the oncogene Akt on various cancers. In prostate cancer (PCa), suppression of Akt activity in the advanced stages promoted transforming growth factor-β (TGFβ) pathway-mediated epithelial-to-mesenchymal transition (EMT) and metastasis to the lungs. In the current study, we performed Affymetrix analysis to compare the expression profile of microRNAs in the mouse prostate tissues collected at the prostatic inter-epithelial neoplasia (PIN) stage from Transgenic adenocarcinoma of the mouse (TRAMP)/Akt1+/+ versus TRAMP/Akt1–/– mice, and at the advanced stage from TRAMP/Akt1+/+ mice treated with triciribine (Akt inhibitor) versus DMSO-treated control. Our analysis demonstrates that in the early stage, Akt1 in the TRAMP prostate tumors express a set of miRNAs responsible for regulating cancer cell survival, proliferation, and tumor growth, whereas, in the advanced stages, a different set of miRNAs that promote EMT and cancer metastasis is expressed. Our study has identified novel Akt-regulated signature microRNAs in the early and advanced PCa and demonstrates their differential effects on PCa growth and metastasis.
KW - Biochemistry
KW - Bioinformatics
KW - Cancer research
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U2 - 10.1016/j.heliyon.2018.e00796
DO - 10.1016/j.heliyon.2018.e00796
M3 - Article
C2 - 30238065
AN - SCOPUS:85053394231
SN - 2405-8440
VL - 4
SP - e00796
JO - Heliyon
JF - Heliyon
IS - 9
M1 - e00796
ER -
