Long noncoding RNA VPS9D1-AS1 promotes the progression of endometrial cancer via regulation of the miR-187-3p/S100A4 axis.

VPS9D1-AS1 functions as an oncogene in many cancers. However, its role and potential mechanism in the progression of endometrial cancer (EC) are not fully understood. VPS9D1-AS1 levels in EC and adjacent normal tissues were investigated using the TCGA-UCEC cohort and 24 paired clinical samples. The roles of VPS9D1-AS1 and miR-187-3p in cell cycle, proliferation, and apoptosis were evaluated by loss- and gain-of-function experiments. In addition, the effect of VPS9D1-AS1 on tumor growth was further investigated in vivo. Rescue experiments were performed to investigate the involvement of the miR-187-3p/S100A4 axis in VPS9D1-AS1 knockdown-mediated antitumor effects. VPS9D1-AS1 was highly expressed in EC tissues. VPS9D1-AS1 knockdown, similar to miR-187-3p overexpression, significantly inhibited cell proliferation, inhibited colony formation, induced cell cycle arrest, and facilitated apoptosis of KLE cells. MiR-187-3p bound directly to VPS9D1-AS1 and the 3'UTR of S100A4. Furthermore, VPS9D1-AS1 negatively regulated miR-187-3p while positively regulating S100A4 expression in EC cells. MiR-187-3p knockdown or S100A4 overexpression partially reversed the tumor suppressive function of VPS9D1-AS1 knockdown. The results suggest that VPS9D1-AS1 affects EC progression by regulating the miR-187-3p/S100A4 axis. This may provide a promising therapeutic target to help treat EC.

LncRNA VPS9D1-AS1 regulates miR-187-3p/fibroblast growth factor receptor-like 1 axis to promote proliferation, migration, and invasion of prostate cancer cells.

The morbidity and mortality of prostate cancer are increasing year by year, and the survival rate of prostate cancer patients after treatment is low. Therefore, investigating the molecular mechanism underlying prostate cancer is crucial for developing effective treatments. Recent studies have shown the important role of long-chain non-coding RNAs (lncRNAs) in tumorigenesis. VPS9D1-AS1 can modulate the progression of multiple cancers, but its molecular action mechanism in prostate cancer remains unknown. This study, therefore, intended to investigate the regulatory mechanism of VPS9D1-AS1 in prostate cancer. First, differentially expressed lncRNAs in prostate cancer were identified through bioinformatics approaches. The target lncRNA for the study was determined by reviewing the relevant literature and its downstream miRNA/mRNA axis was uncovered. Then, quantitative reverse transcription polymerase chain reaction was introduced to assess the expression of VPS9D1-AS1, miR-187-3p, and fibroblast growth factor receptor-like 1 (FGFRL1) at a cellular level, and Western blot was conducted to assess the protein level of FGFRL1 in cells. The results indicated that VPS9D1-AS1 and FGFRL1 were highly expressed in prostate cancer while miR-187-3p was less expressed. Besides, MTT, colony formation, wound healing, and cell invasion assays showed that silencing VPS9D1-AS1 inhibited the viability, migration ability, and invasion ability of prostate cancer cells. Dual-luciferase assay and RNA binding protein immunoprecipitation assay were performed to explore the interplay of miR-187-3p and VPS9D1-AS1 or FGFRL1. The results showed that VPS9D1-AS1 could sponge miR-187-3p, and FGFRL1 could serve as a direct target of miR-187-3p. Moreover, combined with the results of the rescue experiment, VPS9D1-AS1 was found to upregulate FGFRL1 by competitively sponging miR-187-3p to accelerate the malignant behaviors of prostate cancer cells. In conclusion, VPS9D1-AS1 could promote the phenotype progression of prostate cancer cells through targeting the miR-187-3p/FGFRL1 axis, and it has the potential to be a target for prostate cancer patients.

Long non-coding RNA VPS9D1-AS1 facilitates cell proliferation, migration and stemness in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common cancer leading to high morbidity and mortality in worldwide. Previous studies revealed that SEC61 translocon alpha 1 subunit1 (SEC61A) can act as an oncogene in colon adenocarcinoma. However, the functions and molecular mechanism associated with HCC progression remain to be explored. This study aimed at exploring the role of SEC61A1 in HCC progression. METHODS: EdU assay and colony formation assay were applied to assess cell proliferation. The migratory ability of transfected HCC cells was evaluated by transwell migration assay. Sphere formation assay was used to detect the stemneess of HCC cells. Bioinformatics analysis tools and mechanism experiments were used to predict and analyze the potential molecular mechanism associated with the upregulation of SEC61A1 in HCC cells. RESULTS: Up-regulated SEC61A1 facilitated cell proliferation, migration and stemness in HCC cells. MiR-491-5p negatively regulated SEC61A1 and inhibited HCC cell proliferation and migration by targeting SEC61A1. VPS9D1 antisense RNA 1 (VPS9D1-AS1) could up-regulate SEC61A1 through sponging miR-491-5p. Early growth response 1 (EGR1) was identified as the upstream transcriptional activator for both SEC61A1 and VPS9D1-AS1. CONCLUSIONS: Our study unveiled a novel molecular pathway facilitating HCC cell proliferation, migration and stemness, which may shed new insight into HCC treatment.

VPS9D1-AS1 gene rs7206570 polymorphism associated with the clinical stage of colorectal cancer and binding with hsa-miR-361-3p.

VPS9D1-AS1 is a long non-coding RNA that can operate as a competitive endogenous RNA and plays an essential role in the occurrence and development of malignancies, including colorectal cancer (CRC). In this study, we investigated whether a putative functional polymorphism (rs7206570) in the VPS9D1-AS1 gene is linked to the risk and clinical stage of CRC. Sanger sequencing method was used to detect the rs7206570 polymorphism in 500 CRC patients and 500 healthy individuals. Quantitative real-time PCR technology was used to detect the expression of VPS9D1-AS1 and hsa-miR-361-3p in colorectal tissues with different rs7206570 genotypes. The dual-luciferase reporter assay was used to examine whether the rs7206570 polymorphism affects hsa-miR-361-3p binding. The rs7206570 polymorphism was not associated with CRC risk, but was associated with the clinical stage of CRC. CRC patients with rs7206570 A allele were less likely to have high-stage CRC. Furthermore, there was a significant negative correlation between the expression of VPS9D1-AS1 and hsa-miR-361-3p in CRC tissues with rs7206570 GG genotype. Dual-luciferase reporter assay showed that the rs7206570 A allele presumably hinders the binding of VPS9D1-AS1 to hsa-miR-361-3p. In conclusion, VPS9D1-AS1 gene rs7206570 polymorphism affecting hsa-miR-361-3p binding was associated with the clinical stage of CRC, which might be able to assist in the preoperative staging of CRC.

VPS9D1-AS1, a novel long-non-coding RNA, acts as a tumor promoter by regulating the miR-324-5p/ITGA2 axis in colon adenocarcinoma.

BACKGROUND: Colon adenocarcinoma (COAD) is among the most common malignancies worldwide. Elucidating the function and mechanism of action of the lncRNA VPS9D1-AS1 in COAD will be of great value for identifying potential therapeutic targets. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to measure the expression levels of lncRNA VPS9D1-AS1 in COAD tissues and cell lines. After knocking down the expression of VPS9D1-AS1 in two COAD cell lines, namely SW1116 and LoVo, their proliferation rate was measured by the 5-ethynyl-2'-deoxyuridine (Edu) incorporation and cell counting kit-8 (CCK-8) viability assays, migration and invasion abilities were assessed by wound healing and Transwell assays, and apoptosis rate was measured withflow cytometry. Additionally, the dual luciferase reporter assay system was used to investigate the targeting of miR-324-5p to VPS9D1-AS1 and ITGA2 3'-UTR. The inhibitory effects of the miR-324-5p/ITGA2 axis on the function of VPS9D1-AS1 were also examined. In vivo tumorigenesis assay was performed in nude mice injected with VPS9D1-AS1 shRNA or control shRNA lentivirus-transfected LoVo cells. RESULTS: VPS9D1-AS1 was found to be upregulated in COAD tissues and cell lines. VPS9D1-AS1 knockdown inhibited the COAD cell proliferation, migration and invasion and increased the apoptosis rate. In addition, we have demonstrated that miR-324-5p targets VPS9D1-AS1 and ITGA2 3'-UTR, and miR-324-5p silencing or forced ITGA2 expression attenuated the effect of VPS9D1-AS1 knockdown. CONCLUSION: This study identified a novel competing endogenous RNA (ceRNA) pathway that potentially associates with the oncogenic functions of VPS9D1-AS1, miR-324-5p, and ITGA2 in COAD, which could contribute to the identification of new therapeutic approaches targeting COAD.

Long non-coding RNA VPS9D1-AS1 enhances proliferation, invasion, and epithelial-mesenchymal transition in endometrial cancer via miR-377-3p/SGK1.

Endometrial cancer (EC) is a kind of gynecologic malignancy with a rising incidence rate. This study aimed to explore the role of VPS9D1 antisense RNA1 (VPS9D1-AS1) in EC. The expression of VPS9D1-AS1, microRNA (miR)-377-3p, and serum and glucocorticoid-regulated kinase 1 (SGK1) was detected by Quantitative Real-Time PCR (qRT-PCR). Cell proliferation, invasion and epithelial-mesenchymal transition (EMT) were determined by cell counting kit-8 (CCK-8), 5-Ethynyl-2'-Deoxyuridine (EdU) transwell, and western bolt. VPS9D1-AS1 was predicted to sponge miR-377-3p via Starbase, and verified by luciferase reporter, RNA binding protein immunoprecipitation (RIP), and RNA pull-down experiments. The clinical characteristics of VPS9D1-AS1, miR-377-3p, and SGK1 were analyzed. The role of VPS9D1-AS1 on EC tumorigenesis was assessed in xenografted nude mice. VPS9D1-AS1 was upregulated in EC cells and tissues. Interference of VPS9D1-AS1 inhibited growth, invasion, and EMT of EC cells. Mechanically, VPS9D1-AS1 was a molecular sponge of miR-377-3p, and overexpression of miR-377-3p reversed VPS9D1-AS1-induced EC cells proliferation, invasion, and EMT. Moreover, SGK1 was confirmed to bind with miR-377-3p. Furthermore, overexpression of SGK1 alleviated sh-VPS9D1-AS1-caused effects on EC cells. High level of VPS9D1-AS1 and SGK1, or low miR-377-3p expression predicted a poor prognosis. The expression of the three genes was correlated with lymph node metastasis, pathological stage, and International Federation of Gynecology and Obstetrics (FIGO) stage, but not associated with age, ER, and PR expression. Interestingly, knockdown of VPS9D1-AS1 suppressed EC tumor growth in mice. VPS9D1-AS1 promoted cell invasion, proliferation, and EMT via modulating miR-377-3p/SGK1 axis, which provided new options for therapeutic strategies of EC.

LncRNA VPS9D1-AS1 Sponging miR-520a-5p Contributes to the Development of Uterine Corpus Endometrial Carcinoma by Enhancing BIRC5 Expression.

The pattern of VPS9D1-AS1 expression and its effects on uterine corpus endometrial carcinoma (UCEC) remained unclear. VPS9D1-AS1, miR-520a-5p, and BIRC5 mRNA levels were quantified by qRT-PCR. Bax, Bcl-2, N-cadherin, E-cadherin, and BIRC5 protein levels were analyzed through western blotting. Cell migration, invasion, proliferation, as well as apoptosis of cells were checked after performing assay for wound-healing, Transwell, cell-counting kit-8 (CCK-8) assay, and western blotting. VPS9D1-AS1 effects on UCEC were observed in nude mice. Through bioinformatics tools, we analyzed the association present among miR-520a-5p, BIRC5, and VPS9D1-AS1 along with RNA immunoprecipitation, and Dual-Luciferase verification reporter analysis. Our findings suggested VPS9D1-AS1 gene expression was up-regulated in both tissues as well as cells of UCEC. VPS9D1-AS1 knockdown suppressed migration, invasion, epithelial-mesenchymal transition (EMT) along with proliferation of UCEC cells, caused in vitro cell apoptosis initiation, and in vivo reduction of tumor growth. Mechanistically, it was verified that VPS9D1-AS1 targeted BIRC5 and caused miR-520a-5p sponging. Inhibitor of miR-520-5p markedly reversed the anti-tumor effects of VPS9D1-AS1 knockdown or BIRC5 knockdown on UCEC progression. Our studies revealed that VPS9D1-AS1 contributed to the UCEC development and progression by binding to miR-520a-5p competitively and inducing BIRC5 expression, indicating that VPS9D1-AS1 might act as a therapeutic target to develop new therapies for UCEC patients.

The lncRNA VPS9D1-AS1 Promotes Hepatocellular Carcinoma Cell Cycle Progression by Regulating the HuR/CDK4 Axis.

Long noncoding RNAs (lncRNAs) represent promising therapeutic targets associated with hepatocellular carcinoma (HCC). lncRNA VPS9D1 antisense RNA 1 (VPS9D1-AS1) regulates colon and prostate cancer, but its relevance in HCC remains to be clarified. Using microarray data from the NCBI Gene Expression Omnibus (GEO) database (GSE65485) and The Cancer Genome Atlas (TCGA) database, VPS9D1-AS1 expression in HCC and normal liver tissue sample HCC were compared. Relative lncRNA expression was also measured through real-time quantitative PCR (qPCR) in 80 pairs of HCC tumor and paracancerous tissues and in human HCC cell lines. VPS9D1-AS1 knockdown was achieved by transfecting these HCC cells with a specific siRNA construct in vitro, and the proliferation of these cells was quantified through cell proliferation assays and colony formation assays, while flow cytometry was employed to assess their cell cycle progression. The role of the VPS9D1-AS1 lncRNA as a regulator of HCC tumorigenesis was also assessed in vivo by subcutaneously implanting BALB/c nude mice with HepG2 cells stably expressing either sh-VPS9D1-AS1 or a control shRNA construct. Mechanistic analyses were additionally conducted by examining in vitro CDK4 and HuR expression through western blotting and qPCR. VPS9D1-AS1 expression was significantly increased in HCC tissues in the analyzed databases and our independent tissue samples. Elevated VPS9D1-AS1 expression was related to larger tumor size and more advanced tumor, node, metastasis (TNM) stage, and HCC patients expressing higher levels of this lncRNA exhibited poorer survival outcomes. Knocking down VPS9D1-AS1 impaired the proliferative and colony formation activity of HepG2 cells while promoting their apoptotic death. Consistently, VPS9D1-AS1 silencing suppressed HCC tumor growth in vivo. Mechanistically, VPS9D1-AS1 was able to bind to the HuR protein and thereby influence the stability and expression of the CDK4 mRNA, thus impacting HCC cell proliferation. The VPS9D1-AS1/HuR/CDK4 signaling axis regulates HCC tumor cell oncogenic activity, highlighting this pathway as a promising therapeutic target.

Long noncoding RNA VPS9D1-AS1 promotes esophageal squamous cell carcinoma progression via the Wnt/ß-catenin signaling pathway.

The VPS9D1 antisense RNA1 (VPS9D1-AS1, lncRNA MYU) can act as an oncogene or an antioncogene in different malignancies. In the present study, we demonstrated that VPS9D1-AS1 is significantly upregulated in esophageal squamous cell carcinoma (ESCC) and assessed its biological function and clinical prognosis. RNA-sequencing was conducted in four pairs of ESCC tissues and normal adjacent tissues (NATs). Compared with controls, lncRNA VPS9D1-AS1 was highly expressed in ESCC tissues, cell lines and plasma. VPS9D1-AS1 upregulation significantly correlated with the histopathological grade and clinical stage of ESCC. Analyses revealed poor prognosis in ESCC patients with high VPS9D1-AS1 expression. VPS9D1-AS1 knockdown led to the inhibition of tumor proliferation, migration, and invasion in vivo and vitro. VPS9D1-AS1 silencing downregulated the Wnt/ß-catenin signaling pathways by acting on key proteins such as ß-catenin and c-Myc. However, the expressions of these proteins increased after the addition of pathway agonist CT99021. Therefore, taken together VPS9D1-AS1 is highly expressed in ESCC and its expression can lead to poor prognosis. In conclusion, this study suggested that VPS9D1-AS1 acts as a vital part in facilitating ESCC progression and can be a potential biomarker for the diagnosis of patients with ESCC.

LncRNA VPS9D1-AS1 Promotes Malignant Progression of Lung Adenocarcinoma by Targeting miRNA-30a-5p/KIF11 Axis.

Objective: This research probed into the molecular mechanisms of long non-coding RNA (lncRNA) VPS9D1 Antisense RNA 1 (VPS9D1-AS1) in lung adenocarcinoma (LUAD). Methods: lncRNA expression level was evaluated bioinformatically, and its downstream miRNA/mRNA regulatory axis was predicted by bioinformatics methods as well. qRT-PCR was used to measure VPS9D1-AS1, miRNA-30a-5p, and kinesin family member 11 (KIF11) expression. Western blot was performed to measure KIF11 protein expression. Proliferation, migration, and invasion of LUAD cells were all observed by cell biological function experiments. Dual-luciferase assay detected binding between miRNA-30a-5p and VPS9D1-AS1 or KIF11, respectively. RIP experiment detected interaction between VPS9D1-AS1 and miRNA-30a-5p. Results: VPS9D1-AS1 and KIF11 were increased in LUAD, whereas miRNA-30a-5p was decreased. VPS9D1-AS1 promoted the malignant progression of LUAD cells and could sponge miRNA-30a-5p. MiRNA-30a-5p could restore the impact of VPS9D1-AS1 on LUAD cells. KIF11 was a target downstream of miRNA-30a-5p. VPS9D1-AS1 could upregulate KIF11 expression through competitively sponging miRNA-30a-5p, and KIF11 could restore the impact of miRNA-30a-5p on LUAD cells. Conclusion: VPS9D1-AS1 could foster malignant progression of LUAD via regulating miRNA-30a-5p/KIF11 axis, suggesting that VPS9D1-AS1 is key to regulating the malignant progression of LUAD.

Long non-coding RNA VPS9D1-AS1 promotes growth of colon adenocarcinoma by sponging miR-1301-3p and CLDN1.

Colon adenocarcinoma is a frequent malignancy among all colon cancer types. Long non-coding RNAs (lncRNAs) are involved in the progression of colon adenocarcinoma. This study aimed to uncover the molecular mechanism of VPS9D1-AS1 in regulating colon adenocarcinoma development. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) revealed that VPS9D1-AS1 expression was markedly upregulated in colon adenocarcinoma tissues and cell lines. Cell functional experiments showed that knockdown of VPS9D1-AS1 repressed the growth and invasion of colon adenocarcinoma cells but upregulated cell apoptosis. In addition, we confirmed the interaction of VPS9D1-AS1-miR-1301-3p-CLDN1 using a luciferase assay. Downregulation of miR-1301-3p promoted the progression of colon adenocarcinoma cells. In conclusion, VPS9D1-AS1 facilitated cell growth and suppressed apoptosis of colon adenocarcinoma cells by sponging miR-1301-3p and upregulating CLDN1, which may be effective therapeutic strategies for patients with colon adenocarcinoma.

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

Prostate cancer (PCa) is a destructive malignancy with a bad prognosis. LncRNA VPS9D1-AS1 has recently been delineated as an oncogene in some kinds of tumor, whereas, the function of VPS9D1-AS1 in PCa remains to be clarified. In this study, we researched its underlying role in PCa. The expression of VPS9D1-AS1 was conspicuously upregulated in PCa tissues and cells. And absence of VPS9D1-AS1 inhibited cell proliferation, migration and invasion, and promoted cell apoptosis in PCa. In addition, VPS9D1-AS1 overexpression led to opposite results. Furthermore, VPS9D1-AS1/MEF2D could sponge with miR-4739. VPS9D1-AS1/MEF2D and miR-4739 were inversely correlated in tumor cells. And the expression of miR-4739 is markedly downregulated in PCa, meanwhile, that of MEF2D exhibited the opposite tendency. However, MEF2D was positively regulated by VPS9D1-AS1. Moreover, MEF2D upregulation offset the suppressive effects of VPS9D1-AS1 deficiency on cell proliferation, migration and invasion in PCa. Additionally, ZEB1 contained the binding sites of VPS9D1-AS1 promoter, and there existed positive relation between them. Taken together, above results illustrated that ZEB1 activated-VPS9D1-AS1 promotes the tumorigenesis and progression of PCa by sponging miR-4739 to upregulate MEF2D, which offering a new useful reference for studying the development process of PCa.

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.

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 AT-hook 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.

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

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 co-downregulated 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.

LncRNA VPS9D1-AS1 promotes cell proliferation in acute lymphoblastic leukemia through modulating GPX1 expression by miR-491-5p and miR-214-3p evasion.

Alterations in messenger RNAs (mRNAs) of protein-coding genes can influence the malignant behaviors of acute lymphoblastic leukemia (ALL) cells. According to the prediction from The Cancer Genome Atlas (TCGA) database, we discovered that glutathione peroxidase 1 (GPX1) was up-regulated in acute myeloid leukemia (LAML) tissues, which pushed us to explore the feasible role and its related modulatory mechanism of GPX1 in ALL. In this research, we first proved the high expression of GPX1 in ALL cells compared with normal cells. Functional assays further revealed that the proliferation was obstructed and the apoptosis was facilitated in ALL cells with silenced GPX1. Then, both miR-491-5p and miR-214-3p that were down-regulated in ALL cells were affirmed to target GPX1. Subsequently, VPS9D1 antisense RNA 1 (VPS9D1-AS1) was recognized as the upstream regulator of miR-491-5p-miR-214-3p/GPX1 axis in a competing endogenous RNA (ceRNA) model. Importantly, we proved that VPS9D1-AS1 served as a tumor promoter in ALL through elevating GPX1. In conclusion, VPS9D1-AS1 contributed to ALL cell proliferation through miR-491-5p-miR-214-3p/GPX1 axis, hinting an optional choice for the treatment of ALL.

Long noncoding RNA VPS9D1-AS1 overexpression predicts a poor prognosis in non-small cell lung cancer.

Long noncoding RNAs (LncRNAs) have been reported to play vital roles in non-small cell lung cancer (NSCLC). Recently, LncRNA/VPS9D1-AS1 has been reported to be overexpressed in various cancers. In this study, we aimed to investigate its expression pattern and clinical significance and further evaluate its prognostic value for NSCLC. VPS9D1-AS1 expression was examined in 184 NSCLC patients using a highly sensitive in situ hybridization protocol (RNAscope), and the expression values were correlated with the clinicopathological features. Another cohort including 12 NSCLC patients was used to validate the differential expression of VPS9D1-AS1 by qRT-PCR. TCGA datasets were further used to validate the main findings. We found that the levels of VPS9D1-AS1 were significantly higher in cancer tissues than in paired normal tissues from both lung squamous cell carcinoma (SCC) and adenocarcinoma (ADC) (P < 0.001). Importantly, the levels of VPS9D1-AS1 in patients with lung SCC were significantly higher than those in patients with lung ADC. The high levels of VPS9D1-AS1 were found to be associated with cancer lymph node metastasis (P = 0.020). Prognostic analysis revealed that the survival time for SCC patients with high levels of VPS9D1-AS1 was significantly shorter than that of patients with low levels of VPS9D1-AS1 (P = 0.007). Therefore, our findings suggest that the overexpression of VPS9D1-AS1 serves as a promising biomarker to predict the prognosis of NSCLC.

Decreased expression of lncRNA VPS9D1-AS1 in gastric cancer and its clinical significance.

BACKGROUND: A recent study has demonstrated that the long non-coding RNA VPS9D1-AS1 is highly expressed in colorectal cancer and predicts poor prognosis. However, roles of VPS9D1-AS1 in gastric cancer remained poorly understood. OBJECTIVE: The aim of this study is to decipher the expression of VPS9D1-AS1 in gastric cancer (GC) patients, so as to assess whether or not it could be used as a novel biomarker for prognosis in gastric cancer patients. METHODS: The expression of VPS9D1-AS1 was examined in cancer tissues and paired adjacent non-tumorous tissues from 126 gastric cancer patients using qRT-PCR. Correlations between the expression of VPS9D1-AS1 and clinicopathological parameters and patients' survival were analyzed. RESULTS: VPS9D1-AS1 expression was downregulated in gastric cancer tissues than that in adjacent non-tumorous tissues (P< 0.001). VPS9D1-AS1 expression level was markedly correlated with tumor size and TNM stage in gastric cancer. Kaplan-Meier analysis showed low expression of VPS9D1-AS1 were correlated with poor overall and disease free survival. On multivariate analysis, the hazard ratio of VPS9D1-AS expression was 0.30 (95% CI = 0.13-0.66, P= 0.003) for overall survival. CONCLUSIONS: Overall, our data suggest that downregulated VPS9D1-AS1 may be used as a novel prognosis predictor of gastric cancer.