Long Noncoding RNA VPS9D1-AS1 Sequesters microRNA-525-5p to Promote the Oncogenicity of Colorectal Cancer Cells by Upregulating HMGA1

• Main Authors: Liu H, Zhang X, Jin X, Yang Y, Liang G, Ma Y, Wang B
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-10-01
• Series: Cancer Management and Research
• Subjects: vps9d1 antisense rna 1; colorectal cancer; competing endogenous rna model; therapeutic target
• Online Access: https://www.dovepress.com/long-noncoding-rna-vps9d1-as1-sequesters-microrna-525-5p-to-promote-th-peer-reviewed-article-CMAR

Hairui Liu,1 Xueying Zhang,2 Xianmei Jin,3 Yubo Yang,1 Guodong Liang,1 Yuehan Ma,1 Bing Wang4 1Department of Abdominal Surgery, Jilin Cancer Hospital, Changchun, Jilin 130021, People’s Republic of China; 2Department of Oncology Medicine, Jilin Cancer Hospital, Changchun, Jilin 130021, People’s Republic of China; 3Department of Childhood Solid Tumor, First Hospital of Jilin University, Changchun, Jilin 130021, People’s Republic of China; 4Department of Radiotherapy, Jilin Cancer Hospital, Changchun, Jilin 130021, People’s Republic of ChinaCorrespondence: Bing WangDepartment of Radiotherapy, Jilin Cancer Hospital, 1018, Huguang Road, Changchun, Jilin 130021, People’s Republic of ChinaEmail [e-mail]: The long noncoding RNA VPS9D1 antisense RNA 1 (VPS9D1-AS1) has emerged as a critical regulator in non-small-cell lung, gastric, and prostate cancers. In this study, we measured the expression levels of VPS9D1-AS1 in colorectal cancer (CRC) and determined the role of VPS9D1-AS1 in regulating the biological activities of CRC cells. In addition, we thoroughly elucidated the molecular mechanism mediating the oncogenic activities of VPS9D1-AS1 in CRC.Methods: The expression levels of VPS9D1-AS1 in CRC tissues and cell lines were detected via quantitative reverse transcription-polymerase chain reaction. Loss-of-function experiments were performed to detect the effects of VPS9D1-AS1 silencing on CRC cell proliferation, apoptosis, migration, and invasion as well as on tumor growth in vivo. Bioinformatics analysis predicted the potential microRNAs (miRNAs) interacting with VPS9D1-AS1, and this prediction was further confirmed via RNA immunoprecipitation and luciferase reporter assays.Results: Our results demonstrated the upregulated expression of VPS9D1-AS1 in CRC tissues and cell lines. Functionally, VPS9D1-AS1 interference suppressed CRC cell proliferation, migration, and invasion and promoted cell apoptosis in vitro. In addition, the loss of VPS9D1-AS1 hindered tumor growth in vivo. Mechanistic studies identified VPS9D1-AS1 as a competing endogenous RNA in CRC cells, in which VPS9D1-AS1 acted as a molecular sponge of miR-525-5p and consequently increased the expression of high-mobility group AT-hook 1 (HMGA1). Moreover, rescue experiments revealed that the regulatory effects of VPS9D1-AS1 deficiency on CRC cells were abolished after miR-525-5p inhibition or HMGA1 restoration.Conclusion: The newly identified competing endogenous RNA pathway involving VPS9D1-AS1, miR-525-5p, and HMGA1 is implicated in the control of CRC progression and may provide an effective target for CRC diagnosis and therapy.Keywords: VPS9D1 antisense RNA 1, colorectal cancer, competing endogenous RNA model, therapeutic target