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CircRNACCDC66 regulates cisplatin resistance in gastric cancer via the miR-618/BCL2 axis.

Abstract：

:Gastric cancer (GC) remains a serious threat to human health with a high cancer-related death rate and unsatisfactory treatment effects after curative resection, especially with advanced GC. Thus, exploration of the molecular mechanism of cisplatin (CDDP) resistance in GC is crucial. circCCDC66 (hsa_circ_0001313) expression was detected by quantitative reverse-transcription PCR in GC cell lines and tissues. The characteristics of circCCDC66 in CDDP resistance in GC were evaluated in vivo and vitro. We performed luciferin reporter assays, biotin-coupled RNA pull-downs and fluorescence in situ hybridization (FISH) to assess the relationship of miR-618 to circCCDC66. Function was determined by cytotoxicity assay, western immunoblotting and TUNEL. CircCCDC66 was overexpressed in CDDP-resistant cells and tissues. The circCCDC66 expression was significantly associated with malignancy and was an independent risk factor for disease-free survival (DFS) in GC patients treated by CDDP based chemotherapy. Data from in vitro and vivo experiments demonstrated that circCCDC66 inhibited apoptosis by targeting miR-618 and release of B-cell lymphoma-2 (BCL2). CircCCDC66 is an essential regulator in the development of CDDP resistance and may serve as a promising therapeutic target for GC patients. Otherwise, our study adds more evidence of circRNA functioning as a sequestering agent for miRNA.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Zhang Q,Miao Y,Fu Q,Hu H,Chen H,Zeng A,Jin Y,Jiang Y,Qian L,Wu L,Xu L,Wang G,Qiu L,Huang X,Xia Y

doi

10.1016/j.bbrc.2020.03.156

subject

Has Abstract

pub_date

2020-06-04 00:00:00

pages

713-720

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(20)30652-5

journal_volume

526

pub_type

杂志文章

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