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      OncoTargets and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the pathological basis of cancers, potential targets for therapy and treatment protocols to improve the management of cancer patients. Publishing high-quality, original research on molecular aspects of cancer, including the molecular diagnosis, since 2008. Sign up for email alerts here. 50,877 Monthly downloads/views I 4.345 Impact Factor I 7.0 CiteScore I 0.81 Source Normalized Impact per Paper (SNIP) I 0.811 Scimago Journal & Country Rank (SJR)

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      Long noncoding RNA STXBP5-AS1 inhibits cell proliferation, migration, and invasion through inhibiting the PI3K/AKT signaling pathway in gastric cancer cells

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          Abstract

          Introduction

          Poor prognosis of gastric cancer (GC) has partly been a result of late diagnosis due to nonspecific symptoms in the early stages. The overall survival rate of patients with GC is quite low. Here, we presented the functional role and potential mechanism of long noncoding RNA STXBP5-AS1 in GC.

          Materials and methods

          CCK-8, scratch wound healing and Transwell assays were conducted to analyze proliferation, migration, and invasion of SGC7901 and MKN45 cells. Real-time polymerase chain reaction (qPCR) and Western blot assays were performed to investigate the relationship between STXBP5-AS1 and STXBP5. Finally, the correlation between STXBP5-AS1 and phosphorylated AKT1 (p-AKT1) was explored to reveal the potential mechanism of STXBP5-AS1 in GC. Western blot assays were performed to analyze phosphorylated AKT1 (p-AKT1) and AKT levels.

          Results

          Our results suggested that STXBP5-AS1 suppressed proliferation, migration, and invasion, and the upregulation of STXBP5-AS1 significantly repressed STXBP5 expression, and knockdown of STXBP5-AS1 promoted STXBP5 expression. In addition, the p-AKT1 level decreased when STXBP5-AS1 was overexpressed and the p-AKT1 level increased with STXBP5-AS1 knockdown in SGC7901 and MKN45 cells.

          Conclusion

          In summary, our results indicate that STXBP5-AS1 inhibits cell proliferation, migration, and invasion through PI3K/AKT in GC.

          Most cited references17

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          Divergent Routes toward Wnt and R-spondin Niche Independency during Human Gastric Carcinogenesis

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            LncRNA AK023391 promotes tumorigenesis and invasion of gastric cancer through activation of the PI3K/Akt signaling pathway

            Background Patients with gastric cancer commonly have a poor prognosis, owing to its invasiveness and distant metastasis. Recent studies have confirmed the pivotal role of long non-coding RNAs (lncRNAs) in tumorigenesis and the progression of malignant tumors, including gastric cancer. However, little is known about the molecular mechanism by which lncRNA AK023391 contributes to gastric cancer. Methods A lncRNA microarray was used to identify the differentially expressed lncRNA AK023391 in gastric cancer and adjacent normal tissues. In addition, RNA fluorescence in situ hybridization (FISH) was used to investigate the association between AK023391 expression and the clinicopathological characteristics and prognosis of patients with gastric cancer. Subsequently, a series of in vitro assays and a xenograft tumor model were used to observe the functions of lncRNA AK023391 in gastric cancer cells. A cancer pathway microarray, bioinformatic analysis, western blotting, and immunochemistry were carried out to verify the regulation of AK023391 and its downstream PI3K/Akt signaling pathway. Results Expression of lncRNA AK023391 was significantly upregulated in gastric cancer samples and cell lines in comparison to adjacent normal tissues, and was positively correlated with poor survival in patients with gastric cancer. The multivariate Cox regression model revealed that AK023391 expression acted as an independent prognostic factor for survival in patients with gastric cancer. Knockdown of AK023391 inhibited cell growth and invasion both in vitro and in vivo, and induced apoptosis and cell cycle arrest in gastric cancer cells, whereas its overexpression reversed these effects. Mechanistically, PI3K/Akt signaling mediated the NF-κB, FOXO3a, and p53 pathways. Moreover, downstream transcription factors, such as c-myb, cyclinB1/G2, and BCL-6 might be involved in AK023391-induced tumorigenesis in gastric cancer. Conclusions The novel oncogenic lncRNA AK023391 in gastric cancer exerts its effects through activation of the PI3K/Akt signaling pathway, and may act as a potential biomarker for survival in patients with gastric cancer. Electronic supplementary material The online version of this article (10.1186/s13046-017-0666-2) contains supplementary material, which is available to authorized users.
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              Over-expression of lncRNA DANCR is associated with advanced tumor progression and poor prognosis in patients with colorectal cancer.

              Despite advances made in the diagnosis and treatment of human colorectal cancer (CRC), the long-term survival for CRC remains poor. Long non-coding RNA anti-differentiation ncRNA (lncRNA DANCR) was identified to be involved in carcinogenesis of hepatocellular carcinoma. While its expression in CRC and potential role in tumor progression is still unknown. In the present study, we investigated the expression level of lncRNA DANCR as well as its association with CRC progression and prognosis. The expression of lncRNA DANCR was detected by quantitative real-time PCR (qRT-PCR) in 104 CRC specimens. The prognostic value of lncRNA DANCR was further analysis. Our results showed that lncRNA DANCR expression was increased in CRC tissues compared with that in adjacent normal tissues (P<0.05). In addition, tumors with high lncRNA DANCR expression was correlated with TNM stage, histologic grade, and lymph node metastasis (P<0.05). Kaplan-Meier analysis showed that patients with high lncRNA DANCR expression had a shorter overall survival (OS) and disease-free survival (DFS) compared with the low lncRNA DANCR expression group (P<0.05). Moreover, in a multivariate Cox model, our results showed that lncRNA DANCR expression was an independent poor prognostic factor for both OS and DFS in CRC. Our data indicated that lncRNA DANCR expression might be a novel potential biomarker for CRC prognosis.
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                Author and article information

                Journal
                Onco Targets Ther
                Onco Targets Ther
                OncoTargets and Therapy
                OncoTargets and therapy
                Dove Medical Press
                1178-6930
                2019
                08 March 2019
                : 12
                : 1929-1936
                Affiliations
                [1 ]Department of Radiation Oncology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, Guangdong Province, P.R. China
                [2 ]Department of Oncology, The 161th Hospital of Chinese People’s Liberation Army, Wuhan 430010, Hubei Province, P.R. China
                [3 ]Department of Cancer Biotherapy Center, Hubei Cancer Hospital, Wuhan 430079, Hubei Province, P.R. China
                [4 ]Department of Gastroenterology, The 161th Hospital of Chinese People’s Liberation Army, Wuhan 430010, Hubei Province, P.R. China, guokai16824@ 123456163.com
                [5 ]Department of Nuclear Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, Guangdong Province, P.R. China, gysy_zhangjinshan@ 123456163.com
                Author notes
                Correspondence: Jinshan Zhang, Department of Nuclear Medicine, The Third Affiliated Hospital of Guangzhou Medical University, No 63, Duo Bao Road, Liwan District, Guangzhou 510150, Guangdong Province, P.R. China, Tel +86 189 2891 6630, Email gysy_zhangjinshan@ 123456163.com
                Kai Guo, Department of Gastroenterology, The 161th Hospital of Chinese People’s Liberation Army, No 68, Huangpu Avenue, Jiang’an District, Wuhan 430010, Hubei Province, P.R. China, Tel +86 186 9613 6139, Email guokai16824@ 123456163.com
                [*]

                These authors contributed equally to this work

                Article
                ott-12-1929
                10.2147/OTT.S194463
                6415728
                30881044
                95ca861d-9695-4fd3-8cec-3dc54c1c2f43
                © 2019 Cen et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                Original Research

                Oncology & Radiotherapy
                long noncoding rna,stxbp5-as1,stxbp5,pi3k/akt,gc
                Oncology & Radiotherapy
                long noncoding rna, stxbp5-as1, stxbp5, pi3k/akt, gc

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