Dataset Information

MIR497HG-Derived miR-195 and miR-497 Mediate Tamoxifen Resistance via PI3K/AKT Signaling in Breast Cancer.

ABSTRACT: Tamoxifen is commonly used for the treatment of patients with estrogen receptor-positive (ER+) breast cancer, but the acquired resistance to tamoxifen presents a critical challenge of breast cancer therapeutics. Recently, long noncoding RNA MIR497HG and its embedded miR-497 and miR-195 are proved to play significant roles in many types of human cancers, but their roles in tamoxifen-resistant breast cancer remain unknown. The results indicate that MIR497HG deficiency induces breast cancer progression and tamoxifen resistance by inducing downregulation of miR-497/195. miR-497/195 coordinately represses five positive PI3K-AKT regulators (MAP2K1, AKT3, BCL2, RAF1, and CCND1), resulting in inhibition of PI3K-AKT signaling, and PI3K-AKT inhibition in tamoxifen-resistant cells restored tamoxifen responsiveness. Furthermore, ER α binds the MIR497HG promoter to activate its transcription in an estrogen-dependent manner. ZEB1 interacts with HDAC1/2 and DNMT3B at the MIR497HG promoter, resulting in promoter hypermethylation and histone deacetylation. The findings reveal that ZEB1-induced MIR497HG depletion contributes to breast cancer progression and tamoxifen resistance through PI3K-AKT signaling. MIR497HG can be used as a biomarker for predicting tamoxifen sensitivity in patients with ER+ breast cancer.

SUBMITTER: Tian Y

PROVIDER: S-EPMC10131819 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MIR497HG-Derived miR-195 and miR-497 Mediate Tamoxifen Resistance via PI3K/AKT Signaling in Breast Cancer.

Tian Yao Y Chen Zhao-Hui ZH Wu Peng P Zhang Di D Ma Yue Y Liu Xiao-Feng XF Wang Xin X Ding Dan D Cao Xu-Chen XC Yu Yue Y

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20230223 12

Tamoxifen is commonly used for the treatment of patients with estrogen receptor-positive (ER+) breast cancer, but the acquired resistance to tamoxifen presents a critical challenge of breast cancer therapeutics. Recently, long noncoding RNA MIR497HG and its embedded miR-497 and miR-195 are proved to play significant roles in many types of human cancers, but their roles in tamoxifen-resistant breast cancer remain unknown. The results indicate that MIR497HG deficiency induces breast cancer progres ...[more]

PMID: 36815359

Similar Datasets

Project description:BackgroundCircular RNAs (circRNAs) are involved in diverse processes that drive cancer development. However, the expression landscape and mechanistic function of circRNAs in osteosarcoma (OS) remain to be studied.MethodsBioinformatic analysis and high-throughput RNA sequencing tools were employed to identify differentially expressed circRNAs between OS and adjacent noncancerous tissues. The expression level of circ_001422 in clinical specimens and cell lines was measured using qRT-PCR. The association of circ_001422 expression with the clinicopathologic features of 55 recruited patients with OS was analyzed. Loss- and gain-of-function experiments were conducted to explore the role of circ_001422 in OS cells. RNA immunoprecipitation, fluorescence in situ hybridization, bioinformatics database analysis, RNA pulldown assays, dual-luciferase reporter assays, mRNA sequencing, and rescue experiments were conducted to decipher the competitive endogenous RNA regulatory network controlled by circ_001422.ResultsWe characterized a novel and abundant circRNA, circ_001422, that promoted OS progression. Circ_001422 expression was dramatically increased in OS cell lines and tissues compared with noncancerous samples. Higher circ_001422 expression correlated with more advanced clinical stage, larger tumor size, higher incidence of distant metastases and poorer overall survival in OS patients. Circ_001422 knockdown markedly repressed the proliferation and metastasis and promoted the apoptosis of OS cells in vivo and in vitro, whereas circ_001422 overexpression exerted the opposite effects. Mechanistically, competitive interactions between circ_001422 and miR-195-5p elevated FGF2 expression while also initiating PI3K/Akt signaling. These events enhanced the malignant characteristics of OS cells.ConclusionsCirc_001422 accelerates OS tumorigenesis and metastasis by modulating the miR-195-5p/FGF2/PI3K/Akt axis, implying that circ_001422 can be therapeutically targeted to treat OS.

Dataset Information

MIR497HG-Derived miR-195 and miR-497 Mediate Tamoxifen Resistance via PI3K/AKT Signaling in Breast Cancer.

Publications

MIR497HG-Derived miR-195 and miR-497 Mediate Tamoxifen Resistance via PI3K/AKT Signaling in Breast Cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets