The Role Of LncRNA HCP5-encoded Protein In The Resistance Of Breast Cancer Cells To Adriamycin

Objectives: Chemotherapy is a common treatment for breast cancer patients,especially for those with triple-negative breast cancer(TNBC).However,tumor cells are often resistant to cytotoxic drugs,which seriously affects the prognosis and survival time of patients.Some long non-coding RNAs(lnc RNAs)have been discovered to be involved in breast cancer resistance.With the development of proteomic and high-throughput technology,there are some open reading frames(ORFs)found on lnc RNA locus,and their coding products have been proved to work in tumor progression and treatment.So,the aim of this study was to investigate the effect and mechanism of lnc RNA HCP5-encoded protein on Adriamycin sensitivity in breast cancer cells,and to provide references and experimental evidences for clinical treatment.Methods: Coding prediction tools were used to test the existence of ORFs.The breast tissue chips and breast cell lines were used to detect the expression level of lnc RNA HCP5-encoded protein.The knockdown and overexpression of lnc RNA HCP5-ORF were constructed by lentivirus or plasmid transfection in breast cancer cells.The cell proliferation and colony formation were observed to explore the effect of knocking down the coding protein.The growth inhibition rate and half maximal inhibitory concentration of Adriamycin(ADR)were tested by the CCK-8 assay to detect cell sensitivity of ADR.The electron microscopy and confocal imaging were used to detect autophagy formation and lipid reactive oxygen species accumulation.The RNA sequencing and Western blot methods were checked to identify signal pathways.Results: A protein encoded by lnc RNA HCP5,named HCP5-132 aa,is up-regulated in MCF-7ADR-resistant breast cancer cell and TNBC.The colony formation and proliferation are inhibited in breast cancer cells lacking HCP5-132 aa.When knocking down lnc RNA HCP5-encoded protein,there are more autophagic death in cells treated with ADR.The vacuolization and the production of lipid reactive oxygen species also happen simultaneously.The level of autophagy regulatory protein Beclin 1 rises after knocking down HCP5-132 aa,which caused by the phosphorylation of extracellular signal regulated kinase and the activity inhibition of mammalian target of rapamycin.Conclusions: Our study has found that the down-regulation of lnc RNA HCP5-encoded protein is expected to enhance cell sensitivity to ADR,which provides reference and experimental basis for improving the clinical chemotherapy effect of breast cancer.