Androgen receptor (AR) suppresses miRNA-145 to promote renal cell carcinoma (RCC) progression independent of VHL status

Chen, Yuan; Sun, Yin; Rao, Qun; Xu, Hua; Li, Lei; Chang, Chawnshang

doi:10.18632/oncotarget.4522

Cited by 42 publications

(34 citation statements)

References 40 publications

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“…MMP9 is a well-characterized protease with strong proteolytic activity in the ECM [41]. Consistent with our previous studies, we found that MMP9 was a key molecule that mediated AR signals to enhance the metastatic potential of RCC, even though AR might interact with different co-regulators in different microenvironments and cancers [42], [43], [44].…”

Section: Discussionsupporting

confidence: 90%

C1QBP Regulates YBX1 to Suppress the Androgen Receptor (AR)-Enhanced RCC Cell Invasion

et al. 2017

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Early studies suggested that the androgen receptor (AR) might play important roles to promote the renal cell carcinoma (RCC) progression; however, the detailed mechanisms remain unclear. Here we demonstrated the higher YBX1 expression with lower C1QBP expression in human RCC clinical tissues, and the intensity of C1QBP was negatively correlated with the YBX1 nuclear expression. Mechanism dissection found C1QBP could interact with YBX1 to suppress the YBX1 activation via altering the YBX1 phosphorylation and nuclear translocation in RCC cells. The consequences of such suppression of YBX1 might then result in suppressing the RCC cell migration and invasion that involved altering the AR-modulated MMP9 signals. Interruption of this newly identified C1QBP → YBX1 → AR → MMP9-suppressed RCC cell invasion pathway via targeting YBX1 or AR partially reversed the RCC cell invasion. Importantly, results from in vivo mouse model with orthotopic implantation of RCC OSRC2 cells into the left renal capsule also confirmed in vitro cell line studies showing targeting YBX1 could suppress RCC cell invasion via regulation of AR/MMP9 signals. Collectively, these data suggest that C1QBP could regulate YBX1 to suppress the AR-enhanced RCC cell invasion. Targeting this newly identified C1QBP/YBX1/AR/MMP9 signal pathway may provide a new potential therapy to better suppress RCC metastasis.

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Section: Discussionsupporting

confidence: 90%

C1QBP Regulates YBX1 to Suppress the Androgen Receptor (AR)-Enhanced RCC Cell Invasion

et al. 2017

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“…Recently, it has been reported that miRNAs are differently expressed in various human cancers, encompassing RCC and play vital roles in numerous biological process such as cell proliferation, migration, invasion, metastasis and so forth . To date, plenty of miRNAs (including miR‐204, miR‐143/145, miR‐30d and miR‐1826) have been revealed to be the involvement of anti‐tumor progression in RCC patients . Previous studies from our group attest that miR‐646 suppressed RCC cell migration and invasion by targeting NOB1 .…”

Section: Introductionmentioning

confidence: 76%

DNA‐methylation‐mediated repression of miR‐766‐3p promotes cell proliferation via targeting SF2 expression in renal cell carcinoma

Chen

Xue

Zhang

et al. 2017

Intl Journal of Cancer

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Aberrant expression of microRNA (miRNA) emerges as an important role in a wide range of human malignances, and further identification as well as validation of the change of these endogenous non-protein-coding transcripts is warranted. Here, we identify a novel epigenetic regulation of miR-766-3p and investigate its biological function as well as clinical significance in renal cell carcinoma (RCC). Bisulfate analysis elucidates that the promoter of miR-766-3p is highly methylated in RCC tissues compared to non-tumorous tissues. Notably, the downregulation of miR-766-3p is obviously associated with clinical stage and worse prognosis in RCC patients. Upregulated miR-766-3p attenuates cell-cycle progression via targeting SF2 expression and additional SF2/P-AKT/P-ERK signaling pathway. Moreover, high level of SF2, as a novel oncoprotein in RCC, was significantly associated with poor survival in a large cohort of RCC specimens. Taken together, our study presents a road map for the prediction and validation of miR-766-3p/SF2 axis and thus imparts a therapeutic way for further RCC progression.

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“…Currently, enzalutamide is in combination with gemcitabine and cisplatin at phase I clinical trial for the therapy of bladder cancer (NCT02300610). For kidney cancer, AR and AR signaling also play an important role, and the molecular mechanisms have recently been gradually revealed especially by Chang's group . It is proved that an increased AR expression results in higher hematogenous metastasis and lower lymphatic metastasis of clear cell renal cell carcinoma .…”

Section: Ar and Other Cancersmentioning

confidence: 99%

A magic drug target: Androgen receptor

Zhou

Pang

et al. 2018

Medicinal Research Reviews

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Androgen receptor (AR) is closely associated with a group of hormone‐related diseases including the cancers of prostate, breast, ovary, pancreas, etc and anabolic deficiencies such as muscle atrophy and osteoporosis. Depending on the specific type and stage of the diseases, AR ligands including not only antagonists but also agonists and modulators are considered as potential therapeutics, which makes AR an extremely interesting drug target. Here, we at first review the current understandings on the structural characteristics of AR, and then address why and how AR is investigated as a drug target for the relevant diseases and summarize the representative antagonists and agonists targeting five prospective small molecule binding sites at AR, including ligand‐binding pocket, activation function‐2 site, binding function‐3 site, DNA‐binding domain, and N‐terminal domain, providing recent insights from a target and drug development view. Further comprehensive studies on AR and AR ligands would bring fruitful information and push the therapy of AR relevant diseases forward.

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Androgen receptor (AR) suppresses miRNA-145 to promote renal cell carcinoma (RCC) progression independent of VHL status

Cited by 42 publications

References 40 publications

C1QBP Regulates YBX1 to Suppress the Androgen Receptor (AR)-Enhanced RCC Cell Invasion

C1QBP Regulates YBX1 to Suppress the Androgen Receptor (AR)-Enhanced RCC Cell Invasion

DNA‐methylation‐mediated repression of miR‐766‐3p promotes cell proliferation via targeting SF2 expression in renal cell carcinoma

A magic drug target: Androgen receptor

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