LINC01189-miR-586-ZEB1 feedback loop regulates breast cancer progression through Wnt/β-catenin signaling pathway.
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ABSTRACT:
SUBMITTER: Zhang D
PROVIDER: S-EPMC8408558 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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.
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Project description:BackgroundBreast cancer has become the most frequently diagnosed cancer worldwide. Increasing evidence indicated that zinc finger proteins (ZNFs), the largest family of transcription factors, contribute to cancer development and progression. Although ZNF384 is overexpressed in several types of human cancer, the role of ZNF384 in breast cancer remains unknown. Therefore, our research focused on ZNF384 regulation of the malignant phenotype of breast cancer and the underlying molecular mechanisms.MethodsCCK-8 and colony formation assays were used to evaluate cell proliferation. Transwell and scratch assays were used to evaluate the cell migration and invasion. Chromatin immunoprecipitation (ChIP)-qPCR and luciferase reporter assays were used to confirm the target relationship between ZNF384 and zinc finger E-box binding homeobox 1 (ZEB1). Xenografts were used to monitor the targets in vivo effects.ResultsWe noted that ZNF384 was significantly overexpressed in breast cancer and highlighted the oncogenic mechanism of ZNF384. ZNF384 transactivated ZEB1 expression and induced an epithelial and mesenchymal-like phenotype, resulting in breast cancer metastasis. Furthermore, ZNF384 may be a target of miR-485-5p, and ZEB1 can up-regulate ZNF384 expression by repressing miR-485-5p expression. Together, we unveiled a feedback loop of ZNF384-ZEB1 in breast cancer metastasis.ConclusionsThe findings suggest that ZNF384 can serve as a prognostic factor and a therapeutic target for breast cancer patients.
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Project description:BackgroundGlioblastoma has been seen as the most common malignancy of brain tumor. Emerging reports has claimed that SNHG29 (LRRC75A-AS1) was involved in several biological processes via modulation of signaling pathway, and served as an malignant facilitatorin osteosarcoma. However, the specific role of SNHG29 in glioblastoma remains unknown.MethodsRT-qPCR and microarray were operated to measure genes expression. Western blot was performed to examine protein expression. CCK-8 and colony formation assays were used to evaluate cell proliferation. Cell migration was tested by transwell assay. Nuclear-cytoplasmic fractionation was conducted to locate SNHG29. The binding capacity of miR-223-3p to SNHG29 or CTNND1 3'UTR was verified by RIP and luciferase reporter assay.ResultsSNHG29 presented high expression in glioblastoma to boost cell proliferation, migration and EMT process. In addition, miR-223-3p was validated to bind with SNHG29 after prediction and screening. Furthermore, miR-223-3p was proved to be a negative regulator for its target CTNND1. Then, the inhibition on cell proliferation, migration and EMT process resulted from SNHG29 knockdown was recovered by CTNND1 overexpression. At last, the inhibitive impacts on cell proliferation, migration and EMT process of CTNND1 deficiency was abrogated by LiCl.ConclusionsIn conclusion, SNHG29 regulates miR-223-3p/CTNND1 axis to promote glioblastoma progression via Wnt/β-catenin signaling pathway, offering a potential therapeutic point for glioblastoma patients.
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