LncRNA H19 Overexpression Induces Resistance To Bortezomib By Targeting MCL-1 Via MiR-29b-3p In Multiple Myeloma

Objective The study was designed to investigate the clinical value ofLncRNA H19 as a biomarker in the diagnosis,monitoring and prognosis of multiple myeloma,and to explore the molecular mechanism of H19 involved in bortezomib resistance.Methods Serum samples of 80 newly diagnosed patients and 67 normal serum samples were collected,and the expression of H19 in two groups was detected by RT-qPCR.The related clinical indexes of the patients were collected and statistically analyzed.Then,PCR was used to detect the expression of H19 in myeloma cells,and the functions of migration,proliferation,cycle and apoptosis were detected by chamber,CCK8 and flow cytometry respectively.Subsequently,bioinformatics software was used to predict the target molecule miR-29b-3p of H19,and the luciferase reporter gene test was used to confirm the results.Then we perform the related function tests after transfection 0f mir-29b-3p.Next the target protein MCL-1 of miR-29b-3p is predicted by bioinformatics software.Studying the known MCL-1 involved in the control of cell apoptosis,can help tumor cells "hide" drug attack,so we used Western Blot to detect the changes of related apoptosis proteins after drugtreatment.Results The level of LncRNA H19 expression in the serum of first diagnosed patients is higher(P<0.05).Analysis of clinical data shows that H19 expression is associated with bone injury(P<0.05)and total protein level(P<0.05)and helps to assist clinical staging.It is important that the expression of H19 in patients with drug-resistant relapse is significantly higher than that of non drug resistant patients(P<0.05).Cell functions indicate that up regulation of H19 promotes the migration,proliferation and cycle of tumor cells and inhibit apoptosis.The luciferase reporter gene shows that H19 can be combined with miR-29b-3p,thereby promoting the formation of miR-29b-3p target protein MCL-1,and thus inducing resistance to bortezomid.Conclusions 1.Serum lncRNA H19 can be used as an ideal biomarker for MM,assisting diagnosis and monitoring of the dynamic changes of the disease.2.lncRNA H19 inhibits the expression of miR-29b-3p to participate in the malignant progression of multiple myeloma.3.lncRNA H19/miR-29b-3p/MCL-1 control network inhibits apoptosis and participates in the resistance of patients with multiple myeloma to bortezomib.