Androgen receptor regulates SRC expression through microRNA-203

Siu, Man Kit; Chen, Wei Yu; Tsai, Hong Yuan; Yeh, Hsiu Lien; Yin, Juan Juan; Liu, Shih Yang; Liu, Yen-Nien

doi:10.18632/oncotarget.8366

Cited by 13 publications

(11 citation statements)

References 65 publications

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“…Interestingly, AR‐regulated miRNAs are not always oncogenic. For example, AR‐regulated miR‐135a and miR‐203 inhibits PCa cell growth, migration and invasion through downregulating ROCK1/ROCK2 and SRC respectively . In the present study, we demonstrate miR‐193a‐3p is an AR target gene and promotes PCa cell migration through its direct target AJUBA.…”

Section: Discussionsupporting

confidence: 56%

Androgen receptor‐regulated miRNA‐193a‐3p targets AJUBA to promote prostate cancer cell migration

Gui

Zheng

et al. 2017

The Prostate

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Background Dysregulation of microRNA (miRNA) expression is implicated in cancer development and progression by modulating oncogenes or tumor suppressors at the post-transcriptional level. Methods To investigate the role of miRNAs in prostate cancer (PCa) progression, we performed small RNA-sequencing (RNA-seq) analysis in androgen-dependent LNCaP cells and LNCaP-derived castration-resistant prostate cancer (CRPC) C4-2B cells. For functional validation, we specifically investigated miR-193a-3p, which is highly upregulated in C4-2B cells and modulated by the androgen receptor (AR). We elucidated the role of miR-193a-3p and its downstream target gene in PCa cell migration using biochemical approaches. Results We identified a subset of differentially expressed miRNAs in C4-2B cells compared to LNCaP cells. Computational analysis shows that the targets of upregulated miRNAs are significantly associated with downregulated protein-coding mRNAs in C4-2B cells. Gene Ontology analysis further reveals that these downregulated mRNAs are significantly enriched in cell-cell adhesion functions. Downregulation of these miRNA-targeted genes may change PCa cell motility resulting in the acquisition of metastatic potential. We then focus on miR-193a-3p and demonstrate overexpression of miR-193a-3p increases cell migration through downregulating its target AJUBA. AJUBA is a LIM domain protein and contributes to the formation and stability of cadherin-mediated cell-cell adhesion. Loss of AJUBA enhances PCa migration and downregulation of AJUBA expression is observed in metastatic PCa tumors. Conclusions Our results suggest a novel AR/miR-193a-3p/AJUBA pathway implicated in PCa progression. MiR-193a-3p is a potential therapeutic target for metastatic PCa.

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Section: Discussionsupporting

confidence: 56%

Androgen receptor‐regulated miRNA‐193a‐3p targets AJUBA to promote prostate cancer cell migration

Gui

Zheng

et al. 2017

The Prostate

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“…Studies confirmed that targeting SRC by means of a miR-203 mimic could be a hopeful curative approach for SRC signaling-activated PCa treatment (Siu et al, 2016).…”

Section: Mirnas and Resistance To Second-generation Ar Antagonists (Enzalutamide And Abiraterone)mentioning

confidence: 81%

Androgen receptor‐related micro RNAs in prostate cancer and their role in antiandrogen drug resistance

Rezaei

Mahjoubin‐Tehran

Sahebkar

et al. 2019

Journal Cellular Physiology

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Prostate cancer (PCa) is one of the most common cancers and the fifth most common reason for cancer deaths in the males. Surgical castration combined with androgen deprivation therapy, antiandrogens, and androgen synthesis inhibitors is the current therapeutic modalities for PCa. These strategies inhibit androgen synthesis or reduce its binding to the androgen receptor (AR) but the development of resistance to these therapies and transient responsiveness are challenging issues in the treatment of this cancer. Deregulation of ARs has a vital role in the initiation and progression of PCa. Also, recent findings imply that micro RNAs (miRNAs) are involved in the evolution of PCa and mediate drug resistance in different cancers. Hence, discovering and targeting miRNAs might represent a novel therapeutic approach. This review paid particular attention to the AR pathway and existing information on the possible roles of miRNAs associated with AR pathway and drug resistance to two second-generation antiandrogens, that is, enzalutamide and abiraterone.

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“…A reduction in AR-induced miR-203 levels has been associated with an increased growth and migration potential of prostate cancer cells. The dysregulation of the AR signaling in prostate cancer cells results in the over-expression of SRC and enhancement of metastatic ability of these cells [104].…”

Section: Effects Of Circrnas On Armentioning

confidence: 99%

Interaction between Non-Coding RNAs and Androgen Receptor with an Especial Focus on Prostate Cancer

Taheri

Khoshbakht

Jamali

et al. 2021

Cells

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The androgen receptor (AR) is a member of the nuclear receptor superfamily and has three functional domains, namely the N-terminal, DNA binding, and C-terminal domain. The N-terminal domain harbors potent transactivation functions, whereas the C-terminal domain binds to androgens and antiandrogens used to treat prostate cancer. AR has genomic activity being DNA binding-dependent or through interaction with other DNA-bound transcription factors, as well as a number of non-genomic, non-canonical functions, such as the activation of the ERK, AKT, and MAPK pathways. A bulk of evidence indicates that non-coding RNAs have functional interactions with AR. This type of interaction is implicated in the pathogenesis of human malignancies, particularly prostate cancer. In the current review, we summarize the available data on the role of microRNAs, long non-coding RNAs, and circular RNAs on the expression of AR and modulation of AR signaling, as well as the effects of AR on their expression. Recognition of the complicated interaction between non-coding RNAs and AR has practical importance in the design of novel treatment options, as well as modulation of response to conventional therapeutics.

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Androgen receptor regulates SRC expression through microRNA-203

Cited by 13 publications

References 65 publications

Androgen receptor‐regulated miRNA‐193a‐3p targets AJUBA to promote prostate cancer cell migration

Androgen receptor‐regulated miRNA‐193a‐3p targets AJUBA to promote prostate cancer cell migration

Androgen receptor‐related micro RNAs in prostate cancer and their role in antiandrogen drug resistance

Interaction between Non-Coding RNAs and Androgen Receptor with an Especial Focus on Prostate Cancer

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