Dataset Information

LINC01189-miR-586-ZEB1 feedback loop regulates breast cancer progression through Wnt/β-catenin signaling pathway.

ABSTRACT: Non-coding RNAs play essential roles in breast cancer progression by regulating proliferation, differentiation, invasion, and metastasis. However, our understanding of most microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) in breast cancer is still limited. miR-586 has been identified as an important factor in the progression of some types of cancer, but its exact function and relative regulation mechanisms in breast cancer development need to be further investigated. In this study, we showed miR-586 functioned as an oncogene by promoting breast cancer proliferation and metastasis both in vitro and in vivo. Meanwhile, miR-586 induced Wnt/β-catenin activation by directly targeting Wnt/β-catenin signaling antagonists SFRP1 and DKK2/3. Moreover, we demonstrated that LINC01189 functioned as a tumor suppressor and inhibited breast cancer progression through inhibiting an epithelial-mesenchymal transition (EMT)-like phenotype by sponging miR-586. In addition, β-catenin/TCF4 transactivated ZEB1, resulting in a transcriptional repression of LINC01189 expression. In conclusion, our data uncovered the LINC01189-miR-586-ZEB1 feedback loop and provided a novel mechanism participating in the regulation of Wnt/β-catenin signaling in breast cancer progression.

SUBMITTER: Zhang D

PROVIDER: S-EPMC8408558 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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LINC01189-miR-586-ZEB1 feedback loop regulates breast cancer progression through Wnt/β-catenin signaling pathway.

Zhang Di D Liu Xiaofeng X Li Yun Y Sun Li L Liu Shu-Shu SS Ma Yue Y Zhang Huan H Wang Xin X Yu Yue Y

Molecular therapy. Nucleic acids 20210624

Non-coding RNAs play essential roles in breast cancer progression by regulating proliferation, differentiation, invasion, and metastasis. However, our understanding of most microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) in breast cancer is still limited. miR-586 has been identified as an important factor in the progression of some types of cancer, but its exact function and relative regulation mechanisms in breast cancer development need to be further investigated. In this study, we showed ...[more]

PMID: 34513288

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Project description:Drug resistance strikingly limits the therapeutic effect of temozolomide (TMZ) (a common drug for glioma). Long non-coding RNA (lncRNA) RMRP has been found to be implicated in glioma progression. However, the effect of RMRP on TMZ resistance along with related molecular mechanisms is poorly defined in glioma. In the present study, RMRP, ZNRF3, and IGF2BP3 were screened out by bioinformatics analysis. The expression levels of lncRNAs and mRNAs were measured by RT-qPCR assay. Protein levels of genes were detected by western blot and immunofluorescence assays. ZNRF3 mRNA stability was analyzed using Actinomycin D assay. Cell proliferative ability and survival rate were determined by CCK-8 assay. Cell apoptotic pattern was estimated by flow cytometry. The effect of RMRP knockdown on the growth of TMZ-treated glioma xenograft tumors was explored in vivo. The relationships of IGF2BP3, RMRP, and ZNRF3 were explored by bioinformatics prediction analysis, RNA immunoprecipitation, luciferase, and RNA pull-down, and chromatin immunoprecipitation assays. The results showed that RMRP was highly expressed in glioma. RMRP knockdown curbed cell proliferation, facilitated cell apoptosis and reduced TMZ resistance in glioma cells, and hindered the growth of TMZ-treated glioma xenograft tumors. RMRP exerted its functions by down-regulating ZNRF3 in glioma cells. IGF2BP3 interacted with RMRP and ZNRF3 mRNA. IGF2BP3 knockdown weakened the interaction of Argonaute 2 (Ago2) and ZNRF3. RMRP reduced ZNRF3 expression and mRNA stability by IGF2BP3. RMRP knockdown inhibited β-catenin expression by up-regulating ZNRF3. The inhibition of Wnt/β-catenin signaling pathway by XAV-939 weakened RMRP-mediated TMZ resistance in glioma cells. β-catenin promoted RMRP expression by TCF4 in glioma cells. In conclusion, RMRP/ZNRF3 axis and Wnt/β-catenin signaling formed a positive feedback loop to regulate TMZ resistance in glioma. The sustained activation of Wnt/β-catenin signaling by RMRP might contribute to the better management of cancers.

Dataset Information

LINC01189-miR-586-ZEB1 feedback loop regulates breast cancer progression through Wnt/β-catenin signaling pathway.

Publications

LINC01189-miR-586-ZEB1 feedback loop regulates breast cancer progression through Wnt/β-catenin signaling pathway.

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