Long non-coding RNA MYU promotes prostate cancer proliferation by mediating the miR-184/c-Myc axis

Huang

2020

Aging

We investigated the influence of the long noncoding RNA VPS9D1 antisense RNA 1 (VPS9D1-AS1) on the malignant phenotype of non-small cell lung cancer (NSCLC) cells in vitro and in vivo. We also explored the mechanisms by which VPS9D1-AS1 exerts its oncogenic action during NSCLC progression. VPS9D1-AS1 expression was upregulated in NSCLC; the extent of its upregulation significantly correlated with patients' adverse clinicopathological characteristics and shorter overall survival. When VPS9D1-AS1 was knocked down in NSCLC cells, their proliferation, colony-forming capacity, migration, and invasiveness were lower, whereas their apoptosis rate was higher, compared to the control. VPS9D1-AS1 knockdown attenuated tumor growth of NSCLC cells in vivo. Mechanistically, VPS9D1-AS1 directly interacted with microRNA-532-3p (miR-532-3p) in NSCLC cells; the impact of VPS9D1-AS1 knockdown on NSCLC cells was attenuated by miR-532-3p inhibition. Furthermore, VPS9D1-AS1 knockdown decreased the expression of high mobility group AThook 2 (HMGA2) in NSCLC cells via miR-532-3p sponging. Recovery of HMGA2 expression partially reversed the inhibitory effects of VPS9D1-AS1 knockdown on NSCLC cells. Thus, VPS9D1-AS1 functions as a competing endogenous RNA that positively regulates HMGA2 expression by sponging miR-532-3p in NSCLC cells, suggesting that the VPS9D1-AS1-miR-532-3p-HMGA2 pathway can be a potential diagnostic and/or therapeutic target in NSCLC.

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA VPS9D1-AS1 augments the malignant phenotype of non-small cell lung cancer by sponging microRNA-532-3p and thereby enhancing HMGA2 expression

Huang

2020

Aging

“…These exosomal lncRNAs are significantly enriched in target motifs for the miRs, which are found in the same exosomes, suggesting that the sorting of exosomes is a highly organized process that allows for the selection of specific miRs and lncRNAs to be uploaded in their vesicles [184]. It has been reported that exosome-associated lncRNA MYU induces adjacent PCa cell proliferation and migration by competitively binding to miR-184 and therefore upregulates c-Myc [185]. Moreover, urine-derived exosomes collected from PCa patients are enriched in lncRNA-p21, which is associated with the malignancy of PCa [186].…”

Section: The Role Of Exosomes In Shuttling Bioactive Materials Betweementioning

confidence: 99%

“…Affect osteoclastogenesis and osteoblastogenesis and help PCa cells to overcome androgen deprivation in long distant metastasis [180,181,188,189] miR-409, miR-379 and miR-154 Support PCa carcinogenesis and metastasis [177] miR-485-3p Associated with fludarabine resistance in PCa cells [190] H-ras, K-ras (mRNA) Neoplastic transformation of PC patients' adipose stem cells. [130] LincRNA-p21 (lncRNA) Associated with PC malignancy [186] lncRNA MY (lncRNA) Promote adjacent cell proliferation and migration [185] 3.7. Two-Way Crosstalk between Stromal Cells and PCA Cell-Associated Exosomal Cargo…”

Section: Nucleic Acid(s) Biological Function Reference(s)mentioning

confidence: 99%

Exosomes are the Driving Force in Preparing the Soil for the Metastatic Seeds: Lessons from the Prostate Cancer

Saber

Ali

Gaballa

et al. 2020

Cells

Exosomes are nano-membrane vesicles that various cell types secrete during physiological and pathophysiological conditions. By shuttling bioactive molecules such as nucleic acids, proteins, and lipids to target cells, exosomes serve as key regulators for multiple cellular processes, including cancer metastasis. Recently, microvesicles have emerged as a challenge in the treatment of prostate cancer (PCa), encountered either when the number of vesicles increases or when the vesicles move into circulation, potentially with an ability to induce drug resistance, angiogenesis, and metastasis. Notably, the exosomal cargo can induce the desmoplastic response of PCa-associated cells in a tumor microenvironment (TME) to promote PCa metastasis. However, the crosstalk between PCa-derived exosomes and the TME remains only partially understood. In this review, we provide new insights into the metabolic and molecular signatures of PCa-associated exosomes in reprogramming the TME, and the subsequent promotion of aggressive phenotypes of PCa cells. Elucidating the molecular mechanisms of TME reprogramming by exosomes draws more practical and universal conclusions for the development of new therapeutic interventions when considering TME in the treatment of PCa patients.

“…Furthermore, VPS9D1-AS1 level was related to gastric cancer patients' disease-free survival rate (Chen et al, 2017). However, compared with normal prostate tissue or lung tissue, VPS9D1-AS1 was significantly upregulated in cancerous prostate tissue or cancerous non-small cell lung tissue (Wang et al, 2018;Han et al, 2020). These studies showed that VPS9D1-AS1 had different roles in different diseases.…”

Section: Introductionmentioning

confidence: 96%

Chidamide Inhibits Acute Myeloid Leukemia Cell Proliferation by lncRNA VPS9D1-AS1 Downregulation via MEK/ERK Signaling Pathway

Lin

Que

et al. 2020

Front. Pharmacol.

Irregular histone modification and aberrant lncRNAs expression are closely related to the occurrence of tumors including acute myeloid leukemia (AML). However, the effects and specific underlying molecular mechanism of histone deacetylase inhibitors on lncRNA expression in AML cells are unclear. Here, we reported the effects of a novel histone deacetylase inhibitor Chidamide on proliferation and lncRNA expression in AML cells. Chidamide inhibited cell proliferation, blocked G1/S phase transition, and induced cell apoptosis through the caspase-dependent apoptotic pathway in AML cells. Chidamide also inhibited the formation of subcutaneous tumors. Transcriptome sequencing results showed that 1,195 lncRNAs were co-upregulated and 780 lncRNAs were codownregulated after Chidamide treatment of SKM-1 cells and THP-1 cells. Combined with transcriptome sequencing data and the gene expression profiling interactive analysis dataset, we found that VPS9D1-AS1 expression was negatively correlated with the survival of AML patients. VPS9D1-AS1 knockdown inhibited cell proliferation, arrested cell cycle, as well as inhibited the formation of subcutaneous tumors in vivo. VPS9D1-AS1 overexpression had the reverse effect. Furthermore, VPS9D1-AS1 knockdown inhibited the MEK/ERK signaling pathway, and thus enhanced the inhibitory effect of Chidamide on AML cell proliferation. These findings suggested that targeted regulation of VPS9D1-AS1 might overcome the limitations of Chidamide in the treatment of AML.