PTEN公司
舒尼替尼
癌症研究
肾透明细胞癌
肾细胞癌
小RNA
医学
酪氨酸激酶抑制剂
下调和上调
癌症
PI3K/AKT/mTOR通路
肿瘤科
内科学
生物
信号转导
基因
细胞生物学
生物化学
作者
Sang Eun Park,Wonju Kim,Ji-Ye Hong,Dayeon Kang,Seulki Park,Jungyo Suh,Dalsan You,Yun‐Yong Park,Nayoung Suh,Jung Jin Hwang,Choung‐Soo Kim
标识
DOI:10.1038/s41598-022-07468-x
摘要
A multiple receptor tyrosine kinase inhibitor, sunitinib, is a first-line therapy for clear cell renal cell carcinoma (CCRCC). Unfortunately, it has the major challenges of low initial response rate and resistance after about one year of treatment. Here we evaluated a microRNA (miRNA) and its target responsible for sunitinib resistance. Using miRNA profiling, we identified miR-96-5p upregulation in tumors from sunitinib-resistant CCRCC patients. By bioinformatic analysis, PTEN was selected as a potential target of miR-96-5p, which showed low levels in tumors from sunitinib-resistant CCRCC patients. Furthermore, PTEN and miR-96-5p levels were negatively correlated in a large The Cancer Genome Atlas kidney renal clear cell carcinoma cohort and high miR-96 and low PTEN represented poor prognosis in this cohort. Additionally, four-week sunitinib treatment increased miR-96-5p and decreased PTEN only in tumors from a sunitinib-resistant patient-derived xenograft model. We found a novel miR-96-5p binding site in the PTEN 3' UTR and confirmed direct repression by luciferase reporter assay. Furthermore, we demonstrated that repression of PTEN by miR-96-5p increased cell proliferation and migration in sunitinib-treated cell lines. These results highlight the direct suppression of PTEN by miR-96-5p and that high miR-96-5p and low PTEN are partially responsible for sunitinib resistance and poor prognosis in CCRCC.
科研通智能强力驱动
Strongly Powered by AbleSci AI