Dataset Information

Involvement of miR-451 in resistance to paclitaxel by regulating YWHAZ in breast cancer.

ABSTRACT: MicroRNAs (miRNAs) have been identified as major post-transcriptional regulators of the initiation and progression of human cancers, including breast cancer. However, the detail role of miR-451 has not been fully elucidated in breast cancer. In this study, we aimed to investigate the biological role and molecular mechanisms of miR-451 in drug resistance in breast cancer cell lines and in xenograft model. We show that miR-451 is decreased in human breast cancer specimens and in paclitaxel-resistant (PR) cells. Ectopic expression of miR-451 could inhibit the cell migration and invasion, promoted apoptosis, induced cell-cycle arrest Furthermore, tyrosine3-monooxygenase/tryptophan5-monooxygenase activation protein zeta (YWHAZ) was identified as a direct target of miR-451. Remarkably, the expression of YWHAZ is inversely correlated with the level of miR-451 in human breast cancer samples. Co-treatment with miR-451 mimics and YWHAZ-siRNA significantly enhanced YWHAZ knockdown in both SKBR3/PR and MCF-7/PR cells Moreover, miR-451 markedly inhibited expression of ?-catenin via YWHAZ and subsequently inhibited downstream gene cyclin D1, c-Myc expression. The results of xenograft model in vivo showed that intratumor injection of miR-451 agomir induced a tumor-suppressive effect in SKBR3/PR drug-resistant xenograft model. Taken together, our findings suggested that miR-451 might be considered as important and potential target in paclitaxel-resistant breast cancer treatment.

SUBMITTER: Wang W

PROVIDER: S-EPMC5680582 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Involvement of miR-451 in resistance to paclitaxel by regulating YWHAZ in breast cancer.

Wang Wenrui W Zhang Lingyu L Wang Yangyang Y Ding Yongxing Y Chen Tiantian T Wang Yueyue Y Wang Haifeng H Li Yu Y Duan Kecai K Chen Sulian S Yang Qingling Q Chen Changjie C

Cell death & disease 20171005 10

MicroRNAs (miRNAs) have been identified as major post-transcriptional regulators of the initiation and progression of human cancers, including breast cancer. However, the detail role of miR-451 has not been fully elucidated in breast cancer. In this study, we aimed to investigate the biological role and molecular mechanisms of miR-451 in drug resistance in breast cancer cell lines and in xenograft model. We show that miR-451 is decreased in human breast cancer specimens and in paclitaxel-resista ...[more]

PMID: 28981108

Similar Datasets

Project description:Ovarian cancer is the malignant tumor of the female reproductive system with the highest fatality rate. Tolerance to chemotherapeutic drugs such as paclitaxel (PTX) occurring in the very early stage is one of the important factors of the poor prognosis of ovarian cancer. Herein, we aim to study the dysregulation of a particular circular RNA (circRNA), circCELSR1 (hsa_circ_0063809), and its role in the progression and PTX resistance of ovarian cancer. The high expression of circCELSR1 in PTX-resistant tissues of ovarian cancer and PTX-resistant ovarian cancer cells (SKOV3/PTX and HeyA-8/PTX) was determined by microarray analyses and quantitative real-time PCR. Cell Counting Kit-8 (CCK-8) assays were performed to investigate the effect of circCELSR1 on PTX sensitivity of ovarian cancer cells. Flow cytometer assays were used to detect cell cycle and apoptosis of ovarian cancer cells. The effect of circCELSR1 on ovarian cancer cells was assessed in vitro and in vivo. The microRNA (miRNA) sponge mechanism of circRNAs was demonstrated using dual-luciferase reporter and RNA immunoprecipitation assays. By microarray (5 PTX-resistant ovarian cancer tissues ?s 5 PTX-sensitive ovarian cancer tissues) and qRT-PCR (36 normal ovarian tissues and ovarian cancer tissues) we identified circCELSR1 to be dramatically highly expressed in ovarian cancer samples and correlated with PTX resistance. Compared with sensitive cell lines, circCELSR1 was also highly expressed in PTX-resistant ovarian cancer cell lines, and circCELSR1 silencing enhanced PTX-induced cytotoxicity in ovarian cancer cells. Meanwhile, the inhibition of circCELSR1 also caused ovarian cancer cell G0/G1 arrest and an increase in apoptosis. In vivo studies revealed that circCELSR1 was stably inhibited in a xenograft mouse model and inhibited the growth of ovarian cancer. Furthermore, we demonstrated that circCELSR1 acts as a sponge for miR-1252 and verified that forkhead box 2 (FOXR2) is a novel target of miR-1252. In this study, we explored the specific mechanisms of PTX resistance and tumor progress of ovarian cancer due to circCELSR1; presented the circCELSR1-miR-1252-FOXR2 axis and its role in ovarian cancer drug sensitivity and progression; and suggest that the results may provide an experimental basis for clinical application.

Dataset Information

Involvement of miR-451 in resistance to paclitaxel by regulating YWHAZ in breast cancer.

Publications

Involvement of miR-451 in resistance to paclitaxel by regulating YWHAZ in breast cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets