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miR-1343-3p通过直接靶向多发性骨髓瘤细胞中的自噬相关基因7(ATG7)来抑制自噬。

miR‑1343‑3p inhibits autophagy by directly targeting ATG7 in multiple myeloma cells.

作者信息

Guo Yanrong, Ding Xiaoxiao, Dai Changling, Wang Wenwen, Chen Jianlin, Chen Sai, Yang Linjun, Chen Guang

机构信息

Department of Hematology, Taizhou Central Hospital (Taizhou University Affiliated Hospital), Taizhou University, Taizhou, Zhejiang 318008, P.R. China.

Department of Oncology, Municipal Hospital Affiliated to Medical School of Taizhou University, Taizhou, Zhejiang 318002, P.R. China.

出版信息

Biomed Rep. 2024 Oct 4;21(6):185. doi: 10.3892/br.2024.1873. eCollection 2024 Dec.

Abstract

Multiple myeloma (MM) is the second most common type of hematological malignancy globally. Despite application of several new drugs, such as daratumumab, bortezomib/lenalidomide/dexamethasone, in combination with hematopoietic stem cell transplantation, overall prognosis remains poor and the pathological mechanism of MM is still unknown. The present study used TargetScan to predict autophagy-related 7 (ATG7) as a candidate target gene of microRNA (miR)-1343-3p and confirmed the interaction between miR-1343-3p and the ATG7 3' untranslated region (3'UTR) using a dual-luciferase reporter assay. In U266 and RPMI-8226 MM cell lines, miR-1343-3p mimic transfection decreased mRNA and protein levels of ATG7, while miR-1343-3p inhibition increased ATG7 expression levels using reverse transcription-qPCR and western blot analysis. miR-1343-3p mimic transfection inhibited U266 and RPMI-8226 cell survival. Finally, miR-1343-3p regulated ATG7 and autophagy in MM cells using western blot analysis. The present findings suggested that miR-1343-3p may regulate ATG7 and autophagy by directly targeting the 3'UTR of ATG7. To the best of our knowledge, there are no direct data showing the roles of miR-1343-3p in development of MM; however, miR-1343-3p may be considered a potential target for MM treatment.

摘要

多发性骨髓瘤(MM)是全球第二常见的血液系统恶性肿瘤。尽管应用了几种新药,如达雷妥尤单抗、硼替佐米/来那度胺/地塞米松,并联合造血干细胞移植,但总体预后仍然较差,MM的病理机制仍不清楚。本研究使用TargetScan预测自噬相关7(ATG7)为微小RNA(miR)-1343-3p的候选靶基因,并通过双荧光素酶报告基因检测证实了miR-1343-3p与ATG7 3'非翻译区(3'UTR)之间的相互作用。在U266和RPMI-8226 MM细胞系中,转染miR-1343-3p模拟物可降低ATG7的mRNA和蛋白水平,而抑制miR-1343-3p则通过逆转录定量PCR和蛋白质印迹分析提高ATG7的表达水平。转染miR-1343-3p模拟物可抑制U266和RPMI-8226细胞的存活。最后,通过蛋白质印迹分析发现miR-1343-3p在MM细胞中调节ATG7和自噬。本研究结果表明,miR-1343-3p可能通过直接靶向ATG7的3'UTR来调节ATG7和自噬。据我们所知,尚无直接数据表明miR-1343-3p在MM发生发展中的作用;然而,miR-1343-3p可能被视为MM治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42e3/11484188/e14ad2c3c515/br-21-06-01873-g00.jpg

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