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A dual yet opposite growth-regulating function of miR-204 and its target XRN1 in prostate adenocarcinoma cells and neuroendocrine-like prostate cancer cells.

Ding M, Lin B, Li T, Liu Y, Li Y, Zhou X, Miao M, Gu J, Pan H, Yang F, Li T, Liu XY, Li R - Oncotarget (2015)

Bottom Line: Androgen-responsive genes involved in PCa progression including NED remain largely unknown.Importantly, overexpression of miR-204 and knockdown of XRN1 inhibited AR expression in PCa cells.Repression of miR-34a, a known AR-targeting miRNA, contributes AR expression by XRN1.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.

ABSTRACT
Androgen deprivation therapy in prostate cancer (PCa) causes neuroendocrine differentiation (NED) of prostatic adenocarcinomas (PAC) cells, leading to recurrence of PCa. Androgen-responsive genes involved in PCa progression including NED remain largely unknown. Here we demonstrated the importance of androgen receptor (AR)-microRNA-204 (miR-204)-XRN1 axis in PCa cell lines and the rat ventral prostate. Androgens downregulate miR-204, resulting in induction of XRN1 (5'-3' exoribonuclease 1), which we identified as a miR-204 target. miR-204 acts as a tumor suppressor in two PAC cell lines (LNCaP and 22Rv1) and as an oncomiR in two neuroendocrine-like prostate cancer (NEPC) cell lines (PC-3 and CL1). Importantly, overexpression of miR-204 and knockdown of XRN1 inhibited AR expression in PCa cells. Repression of miR-34a, a known AR-targeting miRNA, contributes AR expression by XRN1. Thus we revealed the AR-miR-204-XRN1-miR-34a positive feedback loop and a dual function of miR-204/XRN1 axis in prostate cancer.

No MeSH data available.


Related in: MedlinePlus

miR-204 has a dual regulation on the growth and colony formation of PCa cells(A and B) Cell growth of different PCa cell lines in the presence or absence of miR-204 overexpression by lentivirus. (C) Dual effect of miR-204 overexpression on the colony formation of PCa cells. (D) The effect of a miR-204 inhibitor on the growth of PCa cells. The four cell lines were transfected with the miR-204 inhibitor or a non-targeting control one day after they were seeded in 96-well plates (20 thousand cells each). The cells were used for cell counting 72 hours later. (E-G) The effect of miR-204 overexpression on prostate tumor growth rate in nude mice. 4 day after infected with miR-204-expressing virus or the control virus, 22Rv1 cells (E), CL-1 cells (F) and PC-3 cells (G) (2×106 each) were injected subcutaneously into the right flank of male nude mice (8 mice/group). The tumor volume was measured at the indicated times (data are represented as the mean± SEM; * p<0.05; **p<0.01).
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Figure 2: miR-204 has a dual regulation on the growth and colony formation of PCa cells(A and B) Cell growth of different PCa cell lines in the presence or absence of miR-204 overexpression by lentivirus. (C) Dual effect of miR-204 overexpression on the colony formation of PCa cells. (D) The effect of a miR-204 inhibitor on the growth of PCa cells. The four cell lines were transfected with the miR-204 inhibitor or a non-targeting control one day after they were seeded in 96-well plates (20 thousand cells each). The cells were used for cell counting 72 hours later. (E-G) The effect of miR-204 overexpression on prostate tumor growth rate in nude mice. 4 day after infected with miR-204-expressing virus or the control virus, 22Rv1 cells (E), CL-1 cells (F) and PC-3 cells (G) (2×106 each) were injected subcutaneously into the right flank of male nude mice (8 mice/group). The tumor volume was measured at the indicated times (data are represented as the mean± SEM; * p<0.05; **p<0.01).

Mentions: To investigate whether miR-204 affects the growth of PCa cells, we overexpressed miR-204 in different PCa cells, and our results showed that overexpression of miR-204 inhibited the growth of LNCaP and 22Rv1 cells (Fig. 2A), whereas it stimulated PC-3 and CL1 cell growth (Fig. 2B). Similarly, an opposite effect of miR-204 on the clonogenicity of LNCaP/22Rv1 and PC-3/CL1 cell lines was also observed (Fig. 2C). Moreover, when a miR-204 inhibitor was transfected into cells, it significantly stimulated the growth of LNCaP and 22Rv1 cells, but inhibited the growth of CL1 and PC-3 cells (Fig. 2D). Together, all these results demonstrated that miR-204 plays a dual yet opposite regulatory role in growth of different PCa cells in vitro.


A dual yet opposite growth-regulating function of miR-204 and its target XRN1 in prostate adenocarcinoma cells and neuroendocrine-like prostate cancer cells.

Ding M, Lin B, Li T, Liu Y, Li Y, Zhou X, Miao M, Gu J, Pan H, Yang F, Li T, Liu XY, Li R - Oncotarget (2015)

miR-204 has a dual regulation on the growth and colony formation of PCa cells(A and B) Cell growth of different PCa cell lines in the presence or absence of miR-204 overexpression by lentivirus. (C) Dual effect of miR-204 overexpression on the colony formation of PCa cells. (D) The effect of a miR-204 inhibitor on the growth of PCa cells. The four cell lines were transfected with the miR-204 inhibitor or a non-targeting control one day after they were seeded in 96-well plates (20 thousand cells each). The cells were used for cell counting 72 hours later. (E-G) The effect of miR-204 overexpression on prostate tumor growth rate in nude mice. 4 day after infected with miR-204-expressing virus or the control virus, 22Rv1 cells (E), CL-1 cells (F) and PC-3 cells (G) (2×106 each) were injected subcutaneously into the right flank of male nude mice (8 mice/group). The tumor volume was measured at the indicated times (data are represented as the mean± SEM; * p<0.05; **p<0.01).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4480709&req=5

Figure 2: miR-204 has a dual regulation on the growth and colony formation of PCa cells(A and B) Cell growth of different PCa cell lines in the presence or absence of miR-204 overexpression by lentivirus. (C) Dual effect of miR-204 overexpression on the colony formation of PCa cells. (D) The effect of a miR-204 inhibitor on the growth of PCa cells. The four cell lines were transfected with the miR-204 inhibitor or a non-targeting control one day after they were seeded in 96-well plates (20 thousand cells each). The cells were used for cell counting 72 hours later. (E-G) The effect of miR-204 overexpression on prostate tumor growth rate in nude mice. 4 day after infected with miR-204-expressing virus or the control virus, 22Rv1 cells (E), CL-1 cells (F) and PC-3 cells (G) (2×106 each) were injected subcutaneously into the right flank of male nude mice (8 mice/group). The tumor volume was measured at the indicated times (data are represented as the mean± SEM; * p<0.05; **p<0.01).
Mentions: To investigate whether miR-204 affects the growth of PCa cells, we overexpressed miR-204 in different PCa cells, and our results showed that overexpression of miR-204 inhibited the growth of LNCaP and 22Rv1 cells (Fig. 2A), whereas it stimulated PC-3 and CL1 cell growth (Fig. 2B). Similarly, an opposite effect of miR-204 on the clonogenicity of LNCaP/22Rv1 and PC-3/CL1 cell lines was also observed (Fig. 2C). Moreover, when a miR-204 inhibitor was transfected into cells, it significantly stimulated the growth of LNCaP and 22Rv1 cells, but inhibited the growth of CL1 and PC-3 cells (Fig. 2D). Together, all these results demonstrated that miR-204 plays a dual yet opposite regulatory role in growth of different PCa cells in vitro.

Bottom Line: Androgen-responsive genes involved in PCa progression including NED remain largely unknown.Importantly, overexpression of miR-204 and knockdown of XRN1 inhibited AR expression in PCa cells.Repression of miR-34a, a known AR-targeting miRNA, contributes AR expression by XRN1.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.

ABSTRACT
Androgen deprivation therapy in prostate cancer (PCa) causes neuroendocrine differentiation (NED) of prostatic adenocarcinomas (PAC) cells, leading to recurrence of PCa. Androgen-responsive genes involved in PCa progression including NED remain largely unknown. Here we demonstrated the importance of androgen receptor (AR)-microRNA-204 (miR-204)-XRN1 axis in PCa cell lines and the rat ventral prostate. Androgens downregulate miR-204, resulting in induction of XRN1 (5'-3' exoribonuclease 1), which we identified as a miR-204 target. miR-204 acts as a tumor suppressor in two PAC cell lines (LNCaP and 22Rv1) and as an oncomiR in two neuroendocrine-like prostate cancer (NEPC) cell lines (PC-3 and CL1). Importantly, overexpression of miR-204 and knockdown of XRN1 inhibited AR expression in PCa cells. Repression of miR-34a, a known AR-targeting miRNA, contributes AR expression by XRN1. Thus we revealed the AR-miR-204-XRN1-miR-34a positive feedback loop and a dual function of miR-204/XRN1 axis in prostate cancer.

No MeSH data available.


Related in: MedlinePlus