microRNA-9 Suppresses the Proliferation, Invasion and Metastasis of Gastric Cancer Cells through Targeting Cyclin D1 and Ets1

Zheng, Liduan; Qi, Teng; Yang, Dehua; Qi, Meng; Li, Dan; Xuan, Xuenan; Huang, Kai; Tong, Qiangsong

doi:10.1371/journal.pone.0055719

Cited by 132 publications

(126 citation statements)

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“…Recent studies have demonstrated that cyclinD1 has been associated with tumor invasion and metastasis in clinical studies and in vivo experiments, and cyclin D1 regulates invasion and metastasis through the phosphorylation of paxillin. [24][25][26] In addition to the suppression of cell growth by SOX6 in the ovarian cancer cells, inhibitory effect of SOX6 on ovarian cancer cell invasion was also observed in this study, suggesting that SOX6 may prevent metastasis of ovarian tumors. The SOX family of transcription factors has emerged as modulators of canonical Wnt/β-catenin signaling in diverse development and disease contexts.…”

Section: Discussionsupporting

confidence: 67%

The role of Sox6 and Netrin-1 in ovarian cancer cell growth, invasiveness, and angiogenesis

Xiao

Guo

2017

Tumour Biol.

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SOX6 plays important roles in cell proliferation, differentiation, and cell fate determination. It has been confirmed that SOX6 is a tumor suppressor and downregulated in various cancers, including esophageal squamous cell carcinoma, hepatocellular carcinoma, and chronic myeloid leukemia. Netrin-1 is highly expressed in various human cancers and acts as an anti-apoptotic and proangiogenic factor to drive tumorigenesis. The role of SOX6 and netrin-1 in regulating the growth of ovarian tumor cells still remains unclear. Real-time polymerase chain reaction and western blot were used to determine the SOX6 messenger RNA and protein levels, respectively, in ovarian cancer cells and tumor tissues. Stable transfection of SOX6 was conducted to overexpress SOX6 in PA-1 and SW626 cells. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Invasion of ovarian cancer cells and migration of human umbilical vein endothelial cells were confirmed by Transwell assays. To overexpress netrin-1, ovarian cancer cells with SOX6 restoration was transduced with netrin-1 lentiviral particles. PA-1 xenografts in a nude mice model were used to conduct in vivo evaluation of the role of SOX6 and its relationship with netrin-1 in tumor growth and angiogenesis. In this study, we found significantly reduced SOX6 levels in PA-1, SW626, SK-OV-3, and CaoV-3 ovarian cancer cell lines and human tumor tissues in comparison with normal human ovarian epithelial cells or matched non-tumor tissues. SOX6 overexpression by stable transfection dramatically inhibited proliferation and invasion of PA-1 and SW626 cells. Also, conditioned medium from PA-1 and SW626 cells with SOX6 restoration exhibited reduced ability to induce human umbilical vein endothelial cells migration and tube formation compared with conditioned medium from the cells with transfection control. Furthermore, an inverse relationship between SOX6 and netrin-1 expression was observed in PA-1 and SW626 cells. Overexpression of netrin-1 in ovarian cancer cells with forced SOX6 expression remarkably abrogated the inhibitory effect of SOX6 on proliferation, invasion of the cells, and tumor xenograft growth and vascularity in vivo. Human umbilical vein endothelial cell migration and tube formation were enhanced in the conditioned medium from the ovarian cancer cells transduced with netrin-1 lentivirus particles. Our observations revealed that SOX6 is a tumor suppressor in ovarian cancer cells, and SOX6 exerts an inhibitory effect on the proliferation, invasion, and tumor cell-induced angiogenesis of ovarian cancer cells, whereas nerin-1 plays an opposite role and its expression is inversely correlated with SOX6. Moreover, our findings suggest a new role of SOX6 and netrin-1 for understanding the progression of ovarian cancer and have the potential for the development of new diagnosis and treatment strategies for ovarian cancer.

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Section: Discussionsupporting

confidence: 67%

The role of Sox6 and Netrin-1 in ovarian cancer cell growth, invasiveness, and angiogenesis

Xiao

Guo

2017

Tumour Biol.

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“…miR-9 has also been shown to target CDH-1 mRNA, which downregulated the expression of E-cadherin, thereby increasing the nuclear translocation of β-catenin and enhancing its binding with transcription factors TCF/LEF, in order to upregulate the transcription of genes that facilitate cell proliferation and angiogenesis . Zheng et al (2013) identified cyclin D1 and Ets1 as new targets of miR-9 in gastric cancer; moreover, they demonstrated that miR-9 suppressed the proliferation, invasion, and metastasis of gastric cancer cells. In this study, miR-9 was found to play an oncogenic role in osteosarcoma; however, the precise mechanism with which miR-9 influences osteosarcoma tumorigenesis and progression remains to be understood.…”

Section: Discussionmentioning

confidence: 99%

Pivotal role of microRNA-9 in osteosarcoma tumorigenesis and tumor progression

Wang

et al. 2016

Genet. Mol. Res.

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ABSTRACT. MicroRNA-9 (miR-9) has a well-established role in various tumors; the clinical significance and potential mechanism of miR-9 in human osteosarcoma (OS) has not been elucidated. The aim of this study was to investigate the mechanism and role of miR-9 expression in osteosarcoma cells. miR-9 expression in the OS cell line MG-63 and OS tissues was compared to that in a human osteoblastic cell line (hFOB 1.19) and adjacent normal tissues, respectively, by reverse transcriptase-polymerase chain reaction. miR-9 expression was downregulated by introducing small interfering RNA against miR-9 (si-miR-9) into the cells, and the proliferative, migratory, and invasive capacities of si-miR-9-transfected MG-63 cells were compared to those of control MG-63 cells. miR-9 was significantly upregulated in OS tissues and cell lines compared to the corresponding non-cancerous bone tissues (P < 0.05) and human osteoblastic cell line (P < 0.05), respectively. Upregulated miR-9 expression was also associated with increased cell proliferation (P < 0.05), migration (P < 0.05), and invasion (P < 0.05), and decreased apoptotic ability (P < 0.05). These results suggest that miR-9 may play a pivotal role in tumorigenesis and tumor progression in osteosarcoma.

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“…Interestingly, among the miRNAs that significantly inhibited Salmonella infection by at least 1.5-fold in the screening we found several miRNAs that have been reported to inhibit G1/S transition, namely miR-7, miR-9, miR-26a and miR-26b [28][29][30] . We validated the effect of these miRNAs on Salmonella infection (Fig.…”

Section: Screening For Mirnas Controlling Salmonella Infectionmentioning

confidence: 92%

Functional high-throughput screening identifies the miR-15 microRNA family as cellular restriction factors for Salmonella infection

et al. 2014

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Increasing evidence suggests an important role for miRNAs in the molecular interplay\ud between bacterial pathogens and host cells. Here we perform a fluorescence microscopybased\ud screen using a library of miRNA mimics and demonstrate that miRNAs modulate\ud Salmonella infection. Several members of the miR-15 miRNA family were among the\ud 17 miRNAs that more efficiently inhibit Salmonella infection. We discovered that these\ud miRNAs are downregulated during Salmonella infection, through the inhibition of the\ud transcription factor E2F1. Analysis of miR-15 family targets revealed that derepression of\ud cyclin D1 and the consequent promotion of G1/S transition are crucial for Salmonella\ud intracellular proliferation. In addition, Salmonella induces G2/M cell cycle arrest in infected\ud cells, further promoting its replication. Overall, these findings uncover a mechanism whereby\ud Salmonella renders host cells more susceptible to infection by controlling cell cycle\ud progression through the active modulation of host cell miRNAs

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microRNA-9 Suppresses the Proliferation, Invasion and Metastasis of Gastric Cancer Cells through Targeting Cyclin D1 and Ets1

Cited by 132 publications

References 50 publications

The role of Sox6 and Netrin-1 in ovarian cancer cell growth, invasiveness, and angiogenesis

The role of Sox6 and Netrin-1 in ovarian cancer cell growth, invasiveness, and angiogenesis

Pivotal role of microRNA-9 in osteosarcoma tumorigenesis and tumor progression

Functional high-throughput screening identifies the miR-15 microRNA family as cellular restriction factors for Salmonella infection

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