Unknown

Dataset Information

0

Preclinical studies using miR-32-5p to suppress clear cell renal cell carcinoma metastasis via altering the miR-32-5p/TR4/HGF/Met signaling.


ABSTRACT: While testicular nuclear receptor 4 (TR4) may promote prostate cancer (PCa) metastasis, its role in the clear cell renal cell carcinoma (ccRCC) remains unclear. Here we found a higher expression of TR4 in ccRCC tumors from patients with distant metastases than those from metastasis-free patients, suggesting TR4 may play positive roles in the ccRCC metastasis. Results from multiple in vitro ccRCC cell lines also confirmed TR4's positive roles in promoting ccRCC cell invasion/migration via altering the microRNA (miR-32-5p)/TR4/HGF/Met/MMP2-MMP9 signaling. Mechanism dissection revealed that miR-32-5p could suppress TR4 protein expression levels via direct binding to the 3'UTR of TR4 mRNA, and TR4 might then alter the HGF/Met signaling at the transcriptional level via direct binding to the TR4-response-elements (TR4RE) on the HGF promoter. Then the in vitro data also demonstrated the efficacy of Sunitinib, a currently used drug to treat ccRCC, could be increased after targeting this newly identified miR-32-5p/TR4/HGF/Met signaling. The preclinical study using the in vivo mouse model with xenografted ccRCC cells confirmed the in vitro cell lines data. Together, these findings suggest that TR4 is a key player to promote ccRCC metastasis and targeting this miR-32-5p/TR4/HGF/Met signaling with small molecules including TR4-shRNA or miR-32-5p may help to develop a new therapy to better suppress the ccRCC metastasis.

SUBMITTER: Wang M 

PROVIDER: S-EPMC5938119 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

Preclinical studies using miR-32-5p to suppress clear cell renal cell carcinoma metastasis via altering the miR-32-5p/TR4/HGF/Met signaling.

Wang Mingchao M   Sun Yin Y   Xu Junjie J   Lu Jieyang J   Wang Kefeng K   Yang Dong-Rong DR   Yang Guosheng G   Li Gonghui G   Chang Chawnshang C  

International journal of cancer 20180402 1


While testicular nuclear receptor 4 (TR4) may promote prostate cancer (PCa) metastasis, its role in the clear cell renal cell carcinoma (ccRCC) remains unclear. Here we found a higher expression of TR4 in ccRCC tumors from patients with distant metastases than those from metastasis-free patients, suggesting TR4 may play positive roles in the ccRCC metastasis. Results from multiple in vitro ccRCC cell lines also confirmed TR4's positive roles in promoting ccRCC cell invasion/migration via alterin  ...[more]

Similar Datasets

| S-EPMC7069088 | biostudies-literature
| S-EPMC5077999 | biostudies-literature
| S-EPMC6763763 | biostudies-literature
| S-EPMC7156888 | biostudies-literature
| S-EPMC4652991 | biostudies-literature
| S-EPMC6824104 | biostudies-literature
| S-EPMC6265618 | biostudies-literature
| S-EPMC7901094 | biostudies-literature
| S-EPMC8894382 | biostudies-literature
| S-EPMC4823935 | biostudies-literature