LncRNA MBNL1-AS1 Suppresses Cell Proliferation and Metastasis of Pancreatic Adenocarcinoma through Targeting Carcinogenic miR-301b-3p.

IF 1.4 4区生物学 Q4 GENETICS & HEREDITY Genetics research Pub Date : 2023-03-01 eCollection Date: 2023-01-01 DOI:10.1155/2023/6785005

Chouman Sulidankazha, Alidake, Hai Lin, Tieying He, Wei Han, Qilong Chen

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引用次数: 1

Abstract

Pancreatic adenocarcinoma (PAAD) has been a huge challenge to public health due to its increasing incidence, frequent early metastasis, and poor outcome. The molecular basis of tumorigenesis and metastasis in PAAD is largely unclear. Here, we identified a novel tumor-suppressor long noncoding RNA (lncRNA) MBNL1-AS1, in PAAD and revealed its downstream mechanism. Quantitative real-time PCR (qRT-PCR) data showed that MBNL1-AS1 expression was significantly downregulated in PAAD tissues and cells, which was closely associated with metastasis and poor prognosis. Cell counting kit-8 (CCK-8) assay, transwell assay, and western blot verified that overexpression of MBNL1-AS1 suppressed cell proliferation, migration, and epithelial mesenchymal transformation (EMT) behavior in PAAD cells. By using a dual luciferase reporter gene system, we confirmed that miR-301b-3p was a direct target of MBNL1-AS1. Further mechanismic study revealed that upregulation of miR-301b-3p abolished the inhibitory effect of MBNL1-AS1 overexpression on cell proliferation, tumorigenesis, migration and EMT. Our results demonstrate that MBNL1-AS1 plays a tumor-suppressive role in PAAD mainly by downregulating miR-301b-3p, providing a novel therapeutic target for PAAD.

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LncRNA MBNL1-AS1 通过靶向致癌 miR-301b-3p 抑制胰腺腺癌的细胞增殖和转移

胰腺腺癌（PAAD）发病率越来越高，经常发生早期转移，且预后不佳，因此一直是公共卫生面临的巨大挑战。PAAD 肿瘤发生和转移的分子基础尚不清楚。在这里，我们发现了PAAD中的一种新型肿瘤抑制性长非编码RNA（lncRNA）MBNL1-AS1，并揭示了其下游机制。定量实时 PCR（qRT-PCR）数据显示，MBNL1-AS1 在 PAAD 组织和细胞中的表达显著下调，这与转移和预后不良密切相关。细胞计数试剂盒-8（CCK-8）检测、透孔检测和蛋白印迹证实，过表达 MBNL1-AS1 可抑制 PAAD 细胞的增殖、迁移和上皮间质转化（EMT）行为。通过使用双荧光素酶报告基因系统，我们证实了 miR-301b-3p 是 MBNL1-AS1 的直接靶标。进一步的机理研究发现，miR-301b-3p 的上调可消除 MBNL1-AS1 过表达对细胞增殖、肿瘤发生、迁移和 EMT 的抑制作用。我们的研究结果表明，MBNL1-AS1主要通过下调miR-301b-3p在PAAD中发挥抑瘤作用，为PAAD提供了一个新的治疗靶点。

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来源期刊

Genetics research 生物-遗传学

自引率

6.70%

发文量

审稿时长

>12 weeks

期刊介绍： Genetics Research is a key forum for original research on all aspects of human and animal genetics, reporting key findings on genomes, genes, mutations and molecular interactions, extending out to developmental, evolutionary, and population genetics as well as ethical, legal and social aspects. Our aim is to lead to a better understanding of genetic processes in health and disease. The journal focuses on the use of new technologies, such as next generation sequencing together with bioinformatics analysis, to produce increasingly detailed views of how genes function in tissues and how these genes perform, individually or collectively, in normal development and disease aetiology. The journal publishes original work, review articles, short papers, computational studies, and novel methods and techniques in research covering humans and well-established genetic organisms. Key subject areas include medical genetics, genomics, human evolutionary and population genetics, bioinformatics, genetics of complex traits, molecular and developmental genetics, Evo-Devo, quantitative and statistical genetics, behavioural genetics and environmental genetics. The breadth and quality of research make the journal an invaluable resource for medical geneticists, molecular biologists, bioinformaticians and researchers involved in genetic basis of diseases, evolutionary and developmental studies.