ZEB1 activated-VPS9D1-AS1 promotes the tumorigenesis and progression of prostate cancer by sponging miR-4739 to upregulate MEF2D

Wang, Xiaobin; Chen, Qiangjun; Wang, Xi; Li, Wensheng; Yu, Guoqiang; Zhu, Zhiyi; Zhang, Weitao

doi:10.1016/j.biopha.2019.109557

Cited by 40 publications

(37 citation statements)

References 29 publications

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“…21,22 Patients with nonsmall-cell lung cancer exhibiting high VPS9D1-AS1 expression show shorter overall survival periods compared with those with low VPS9D1-AS1 expression. 21,22 Overexpressed VPS9D1-AS1 has also been confirmed in patients with gastric 23 and prostate 24 cancers. Functionally, VPS9D1-AS1 performs oncogenic actions in non-smallcell lung, 21,22 gastric, 23 and prostate 24 cancers.…”

Section: Discussionmentioning

confidence: 91%

“…21,22 Overexpressed VPS9D1-AS1 has also been confirmed in patients with gastric 23 and prostate 24 cancers. Functionally, VPS9D1-AS1 performs oncogenic actions in non-smallcell lung, 21,22 gastric, 23 and prostate 24 cancers. However, whether VPS9D1-AS1 is differentially expressed in CRC and whether it regulates cancer progression require further investigation.…”

Section: Discussionmentioning

confidence: 91%

“…VPS9D1-AS1 has been reported to control the progression of non-small-cell lung, 21,22 gastric, 23 and prostate 24 cancers. However, the expression status and roles of VPS9D1-AS1 in CRC remain unknown.…”

Section: Introductionmentioning

confidence: 99%

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

Liu

Zhang

Jin

et al. 2020

CMAR

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Background: 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 AThook 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.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 91%

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

Liu

Zhang

Jin

et al. 2020

CMAR

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“…Thus, we further investigated the underlying ceRNA network of LINC00504 in TNBC. Our ndings showed that LINC00504 acted as a molecular sponge of miR-4739., whose expression is negatively regulated by VPS9D1-AS1 in prostate cancer cells [25]. Moreover, other two investigations have documented the functions of miR-4739, which is associated with unilineage hematopoietic stem cell differentiation, the β-catenin signaling pathway and gastric cancer, as well as in the pathogenesis of negative anaplastic large cell lymphoma [26,27].…”

Section: Discussionmentioning

confidence: 99%

The LINC00504/Mir-4739/KLK4 Axis Facilitates Cell Proliferation and Suppresses Cell Apoptosis Through Triggering The Wnt/Β-Catenin Pathway In Triple-Negative Breast Cancer Cells

Wu¹,

Jia²,

Zhang³

et al. 2020

Preprint

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Background: Currently, long non-coding RNAs (lncRNAs) have been validated to exert critical influence on the malignant progression of triple-negative breast cancer (TNBC). LncRNA long intergenic non-protein coding RNA 504 (LINC00504) has been recently reported as a tumor facilitator in the cellular processes of several cancers. However, its function in TNBC remains unknown.Methods: CCK-8 and colony formation assays were used to detect the cell viability and proliferation in TNBC. Flow cytometry analysis was utilized to measure the cycle and apoptosis of TNBC cells. The levels of key proteins associated with cell apoptosis or the β-catenin pathway were detected through western blot analysis. The activity of the Wnt/β-catenin signaling pathway was measured by the TOP/FOP flash assay. ChIP assay was conducted to confirm the binding between LINC00504 and its transcription factor signal transducer and activator of transcription 3 (STAT3). RIP and luciferase reporter assays were used to detect and verify the interaction among LINC00504 and its downstream molecule.Results: LncRNA LINC00504 was upregulated in TNBC, and silenced LINC00504 suppressed cell proliferation and triggers cell cycle arrest at G0/G1 stage and cell apoptosis in TNBC cells. STAT3 can transcriptionally activate LINC00504 and LINC00504 served as a molecular sponge of microRNA (miR-4379). Kallikrein related peptidase 4 (KLK4) was the target gene of miR-4379 and activates the Wnt/β-catenin pathway. LINC00504 upregulated KLK4 via competitively binding with miR-4379 to activate the Wnt/β-catenin pathway in TNBC. The suppression on TNBC cell proliferation and the promotion on TNBC cell cycle arrest and apoptosis under LINC00504 knockdown were rescued by miR-4379 depletion or KLK4 overexpression.Conclusions: The LINC00504/miR-4379/KLK4 axis promotes cell growth and cell cycle progression as well as suppresses cell apoptosis through activating the Wnt/β-catenin pathway.

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“…Additionally, zinc finger E-box binding homeobox 1 (ZEB1) is an upstream mediator of EMT and contributes to the metastasis and invasion of cancer cells via the induction of EMT [ 218 , 219 ]. Accumulating data demonstrate that ZEB1 has high expression in PCa cancer cells and is correlated with the progression and metastasis of these cancer cells [ 220 , 221 ]. Cyclodextrin nanoparticles were designed for the delivery of siRNA-ZEB1 and siRNA-NRP-1 in PCa therapy.…”

Section: Nano-vehiclesmentioning

confidence: 99%

Progress in Delivery of siRNA-Based Therapeutics Employing Nano-Vehicles for Treatment of Prostate Cancer

et al. 2020

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Prostate cancer (PCa) accounts for a high number of deaths in males with no available curative treatments. Patients with PCa are commonly diagnosed in advanced stages due to the lack of symptoms in the early stages. Recently, the research focus was directed toward gene editing in cancer therapy. Small interfering RNA (siRNA) intervention is considered as a powerful tool for gene silencing (knockdown), enabling the suppression of oncogene factors in cancer. This strategy is applied to the treatment of various cancers including PCa. The siRNA can inhibit proliferation and invasion of PCa cells and is able to promote the anti-tumor activity of chemotherapeutic agents. However, the off-target effects of siRNA therapy remarkably reduce its efficacy in PCa therapy. To date, various carriers were designed to improve the delivery of siRNA and, among them, nanoparticles are of importance. Nanoparticles enable the targeted delivery of siRNAs and enhance their potential in the downregulation of target genes of interest. Additionally, nanoparticles can provide a platform for the co-delivery of siRNAs and anti-tumor drugs, resulting in decreased growth and migration of PCa cells. The efficacy, specificity, and delivery of siRNAs are comprehensively discussed in this review to direct further studies toward using siRNAs and their nanoscale-delivery systems in PCa therapy and perhaps other cancer types.

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ZEB1 activated-VPS9D1-AS1 promotes the tumorigenesis and progression of prostate cancer by sponging miR-4739 to upregulate MEF2D

Cited by 40 publications

References 29 publications

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

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

The LINC00504/Mir-4739/KLK4 Axis Facilitates Cell Proliferation and Suppresses Cell Apoptosis Through Triggering The Wnt/Β-Catenin Pathway In Triple-Negative Breast Cancer Cells

Progress in Delivery of siRNA-Based Therapeutics Employing Nano-Vehicles for Treatment of Prostate Cancer

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