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LncRNA FIRRE regulated endometrial cancer radiotherapy sensitivity via the miR-199b-5p/SIRT1/BECN1 axis-mediated autophagy

Junhong Cai, Ru Wang, Yaxiong Chen, Chen Zhang, Lanyan Fu, Cunfu Fan

2023Genomics16 citationsDOIOpen Access PDF

Abstract

BACKGROUND: Endometrial cancer (EC) poses a serious threat to women's health. Radiotherapy has been widely used for EC treatment. However, the mechanism of FIRRE in EC development and radioresistance remains unknown. METHODS: MTT and colony formation assays determined cell proliferation. The degree of autophagy was tested by the measurement of autophagy-related genes and immunofluorescence staining of LC3. Molecular interactions were demonstrated via luciferase reporter assay, RIP, and Co-IP. The FIRRE role's was analyzed by in vivo xenograft tumor model. RESULTS: FIRRE and SIRT1 were upregulated in EC tumor tissues, whereas miR-199b-5p was reduced. FIRRE knockdown increased EC cell radiotherapy sensitivity by sponging miR-199b-5p and inhibiting autophagy. SIRT1 was targeted and negatively regulated by miR-199b-5p. SIRT1 could otherwise deacetylate BECN1 protein and participate in FIRRE-mediated autophagy. Silencing FIRRE increased sensitivity of EC radiotherapy in vivo. CONCLUSION: FIRRE reduced EC cell radiotherapy sensitivity by stimulating autophagy via miR-199b-5p/SIRT1/BECN1 axis.

Topics & Concepts

BECN1AutophagyCancer researchGene knockdownGene silencingEndometrial cancerCell growthDownregulation and upregulationBiologyIn vivoTransfectionCellCell cultureCancerApoptosisGeneBiochemistryGeneticsBiotechnologyCancer-related molecular mechanisms researchCircular RNAs in diseasesAutophagy in Disease and Therapy