MiRNA-516a promotes bladder cancer metastasis by inhibiting MMP9 protein degradation via the AKT/FOXO3A/SMURF1 axis
作者单位：Wenzhou Medical University
会议名称：《2021年中国肿瘤标志物学术大会暨第十五届肿瘤标志物青年科学家论坛》
会议日期：2021年
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
关 键 词：bladder cancer metastasis migration and invasion miR-516a PHLPP2
摘 要：Background: Metastasis is the leading cause of death in patients with bladder cancer(BC).However,current available treatments exert little effects on metastatic BC. Moreover, traditional grading and staging have only alimited ability to identify metastatic BC. Accumulating evidence indicates that the aberrant expression of microRNA is intimately associated with tumor *** far, many miRNAs have been identified as molecular targets for cancer diagnosisand therapy. This study focused on the role of miR-516 a-5 p(miR-516 a) in ***: MiR-516 a expression and its downstream signaling pathway were detected using molecular cell biology and biochemistry approaches and *** clinical BC tissue was used to study the clinic opathological characteristics of patients with different mi R-516 a expression. The biological functions of miR-516 a in BC were tested both in vivo and in ***: A more invasive BC phenotype was significantly and positively correlated with miR-516 a overexpression in BC patients. Mi R-516 a inhibition significantly decreased BC cell invasion and migration in vitro and in vivo. Furthermore, miR-516 a attenuated the expression of PH domain leucine-rich repeat-containing protein phosphatase 2 protein and inhibited SMAD-specific E3 ubiquitin protein ligase 1 transcription by activating the AKT/Forkhead box O3 signaling pathway,which stabilized MMP9 and slowed down its proteasomal degradation, ultimately promoting BC motility and ***: Our findings reveal the crucial function of miR-516 a in promoting BC metastasis, and elucidate the molecular mechanism involved,suggesting that miR-516 a may be a promising novel diagnostic and therapeutic target for BC.