Siva 1 inhibits proliferation, migration and invasion by phosphorylating Stathmin in ovarian cancer cells.
Ontology highlight
ABSTRACT:
SUBMITTER: Ma Y
PROVIDER: S-EPMC5529897 | biostudies-other | 2017 Aug
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Butyrophilin Subfamily 3 Member A3 (BTN3A3) is a type I transmembrane protein belonging to the immunoglobulin (Ig) superfamily, which is expressed in many cancers. Clinical data show that ovarian cancer patients with high expression of BTN3A3 have a longer survival time, but the mechanism of BTN3A3 in the occurrence and progression of ovarian cancer is still unclear. Here, we found that BTN3A3 knockdown can promote the proliferation, migration and invasion of ovarian cancer cells, while overexpression of BTN3A3 can inhibit the proliferation, migration and invasion of ovarian cancer cells. We analyzed the immunoprecipitated BTN3A3 complex by mass spectrometry and found that BTN3A3 binds to FGF2, and the overexpression of BTN3A3 leads to a decrease in the protein level of FGF2, which in turn leads to a decrease in the level of phosphorylation of ERK1/2. By increasing the protein level of FGF2, it was found that the level of ERK1/2 phosphorylation also increased. Finally, the cancer promotion phenomenon caused by BTN3A3 knockdown can be improved by using ERK1/2 inhibitor SCH772984. To sum up, BTN3A3 interacts with FGF2, which inhibits FGF2/ERK1/2 axis and ultimately inhibits the proliferation, migration and invasion of ovarian cancer cells. Our results suggest that BTN3A3 may be a prognostic marker and a potential therapeutic target for ovarian cancer.
| S-EPMC9428752 | biostudies-literature
Project description:MicroRNA-21 is overexpressed in most cancers and has been implicated in tumorigenesis. Accumulating evidence supports a central role for the miR-21 guide strand (miR-21-5p) in ovarian cancer initiation, progression, and chemoresistance. However, there is limited information regarding the biological role of the miR-21 passenger strand (miR-21-3p) in ovarian cancer cells. The aim of this study was to investigate the role of miR-21-3p and its target genes in cisplatin-resistant ovarian cancer cells. Expression profiling of miR-21-5p and miR-21-3p was performed in a panel of cancer cells by qPCR. Colony formation and invasion assays were carried out on ovarian and prostate cancer cells transfected with miR-21-5p and miR-21-3p inhibitors. Dual luciferase reporter assays were used to identify the miR-21-3p target genes in ovarian cancer cells. Our results show that miR-21-5p had higher expression levels compared to miR-21-3p on a panel of cancer cells. Moreover, inhibition of miR-21-5p or miR-21-3p resulted in a significant decrease in ovarian and prostate cancer cell proliferation and invasion. Luciferase reporter assays identify RNA Binding Protein with Multiple Splicing (RBPMS), Regulator of Chromosome Condensation and POZ Domain Containing Protein 1 (RCBTB1), and Zinc Finger protein 608 (ZNF608) as miR-21-3p target genes. SiRNA-induced RBPMS silencing reduced the sensitivity of ovarian cancer cells to cisplatin treatment. Immunohistochemical analyses of serous ovarian cancer patient samples suggest a significant decrease of RBMPS levels when compared to normal ovarian epithelium. Taken together, the data generated in this study suggests a functional role for miR-21-3p in ovarian cancer and other solid tumors.
| S-EPMC5095003 | biostudies-literature
Project description:Tryptophan 2,3‑dioxygenase (TDO2) is a key rate‑limiting enzyme in the kynurenine pathway and promotes tumor growth and escape from immune surveillance in different types of cancer. The present study aimed to investigate whether TDO2 serves a role in the development of ovarian cancer. Reverse transcription‑quantitative PCR and western blotting were used to detect the expression of TDO2 in different cell lines. The effects of TDO2 overexpression, TDO2 knockdown and TDO2 inhibitor on ovarian cancer cell proliferation, migration and invasion were determined by MTS, colony formation and Transwell assays. The expression of TDO2 in ovarian cancer tissues, normal ovarian tissues and fallopian tube tissues were analyzed using the gene expression data from The Cancer Genome Atlas and Genotype‑Tissue Expression project. Immune cell infiltration in cancer tissues was evaluated using the single sample gene set enrichment analysis algorithm. The present study found that RasV12‑mediated oncogenic transformation was accompanied by the upregulation of TDO2. In addition, it was demonstrated that TDO2 was upregulated in ovarian cancer tissues compared with normal ovarian tissues. TDO2 overexpression promoted proliferation, migration and invasion of ovarian cancer cells, whereas TDO2 knockdown repressed these phenotypes. Treatment with LM10, a TDO2 inhibitor, also repressed the proliferation, migration and invasion of ovarian cancer cells. The present study indicated that TDO2 can be used as a new target for the treatment of ovarian cancer.
| S-EPMC8060793 | biostudies-literature
Project description:Ovarian cancer remains the most lethal gynecological malignant tumor. In this study, 24 xanthones were isolated and identified from the pericarps of mangosteen (Garcinia mangostana), and their anti-proliferative activities were tested in ovarian cancer cells. Garcinone E (GE) was found to exhibit excellent anti-proliferative effects among the tested xanthones. It significantly inhibited the proliferation in HEY, A2780, and A2780/Taxol cells as evidenced by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release assay, Hoechst 33342 staining, annexin V/PI staining, and JC-1 staining. It induced endoplasmic reticulum (ER) stress and activated the protective inositol-requiring kinase (IRE)-1α pathway. Knocking down IRE-1α further activated the caspase cascade and caused an increase in cell death. Moreover, GE eliminated the migratory ability of HEY cells by reducing the expression of RhoA and Rac. It also blocked the invasion, which might be related to downregulation of matrix metalloproteinases (MMPs), i.e., MMP-9 and MMP-2, and upregulation of tissue inhibitors of metalloproteinase (TIMP) -1 and TIMP-2. In summary, GE exerts anticancer activities by inducing apoptosis and suppressing migration and invasion in ovarian cancer cells, which indicates its therapeutic potential for ovarian cancer.
| S-EPMC5587559 | biostudies-literature
Project description:To evaluate the role of DiGeorge Critical Region 8 (DGCR8), a key component of miRNA biogenesis pathway in ovarian cancer.The expression of DGCR8 in ovarian cancer was detected by immunostaining and DGCR8 knockdown in ovarian cancer cells was achieved using lentiviral shRNA. Differential expression of miRNAs was determined using Nanostring miRNA arrays and validated by real-time RT-PCR.DGCR8 was highly expressed in ovarian cancer. Knockdown of DGCR8 expression inhibits cell proliferation, migration, and invasion, as well as sensitizes cells to apoptosis induced by the chemotherapeutic drug cisplatin. Cellular survival pathways including ERK1/2 mitogen-activated protein kinase and phosphatidylinositol 3-kinase/AKT were attenuated in DGCR8 knockdown cells. DGCR8 knockdown results in dysregulated miRNA gene expression. miR-27b was identified as the most highly down-regulated miRNA in DGCR8 knockdown cells and promoted cell proliferation in ovarian cancer cells.DGCR8 functions as an oncogene in ovarian cancer, which is in part mediated by miR-27b.
| S-EPMC3984613 | biostudies-literature
Project description:ObjectiveOvarian cancer (OC) is a major threat to women's health. Mesenchymal stem cells (MSCs) are key regulators in cellular communication by secreting extracellular vesicles (EVs) that are involved in OC. This study probed into the mechanism of human MSCs derived-EVs (hMSC-EVs) in regulating OC cell growth and chemotherapy resistance.MethodshMSCs and EVs were isolated and identified. After adding EVs, the uptake of EVs by OC CAOV3/ES2 cells (for in vitro studies), and cell proliferation, migration, and invasion were detected. Downregulated miRNAs in hMSC-EVs were screened and miR-18a-5p expression in OC patients was detected. The prognosis of OC patients was analyzed. Binding sites of miR-18a-5p and NACC1 were predicted and validated. NACC1 expression in OC tissues was measured by RT-qPCR, and its correlation with miR-18a-5p was analyzed by Pearson method. AKT/mTOR pathway activation was assessed by WB. The cisplatin sensitivity of EVs-treated CAOV3 cells was evaluated via MTT assay and tested by tumor formation assay in nude mice.ResultshMSC-EVs suppressed OC cell proliferation, migration, and invasion. miR-18a-5p was downregulated in OC and miR-18a-5p low expression was associated with a poor prognosis. EV-encapsulated miR-18a-5p targeted NACC1. NACC1 was upregulated in OC tissues. miR-18a-5p knockdown and NACC1 overexpression both annulled the inhibition of hMSC-EVs on OC cell growth. AKT and mTOR were elevated in OC and NACC1 activated the AKT/mTOR pathway in OC cells. hMSC-EVs promoted cisplatin sensitivity of OC cells by carrying miR-18a-5p.ConclusionhMSC-EVs-derived miR-18a-5p inhibits OC cell proliferation, migration, invasion, and chemotherapy resistance.
| S-EPMC9172103 | biostudies-literature
Project description:PurposeThe aim of this study was to investigate the expression of stathmin 1 (STMN1) in ovarian cancer and its effect on prognosis. The effect and mechanism of STMN1 on the proliferation and migration of ovarian cancer cells were also investigated.MethodsExpression of STMN1 was measured by immunohistochemical staining in ovarian cancer tissues. The effects of STMN1 on the proliferation and migration capacity of ovarian cancer were evaluated using Cell Counting Kit-8 (CCK-8) assays, colony formation assays, immunofluorescence staining, wound healing assays, and Transwell assays. Transcription factors were predicted by bioinformatic analysis of TCGA database.ResultsSTMN1 was upregulated in ovarian cancer tissues as compared to paracancerous tissues and associated with shorter overall survival. STMN1 expression significantly correlated with FIGO staging and tumor differentiation (P < 0.05). Furthermore, STMN1 promoted proliferation and migration in ovarian cancer cell lines. Bioinformatic analysis revealed that STMN1 was potentially regulated by E2F transcription factors. Then, we found that E2F1 regulated the expression of STMN1 and affected proliferation.ConclusionSTMN1 is overexpressed in ovarian cancer, and its high expression suggests a poor prognosis. STMN1 promotes the proliferation and migration of ovarian cancer and is regulated by E2F1. Thus, STMN1 may serve as a negative prognostic factor and possible target for the treatment of ovarian cancer patients.
| S-EPMC8849943 | biostudies-literature
Project description:BACKGROUND: Epithelial ovarian cancer (EOC) is still a major gynecologic problem with poor 5 year survival rate due to distance metastases, despite routine surgery and chemotherapy. The precise underlying molecular mechanisms that trigger EOC migration and invasion are unclear. Recent studies suggest that the expression of microRNAs is widely dysregulated in ovarian cancer; and that they have evolved into tumorigenic processes, including cell proliferation, apoptosis and motility. METHODS: The expression of miR-124 was assessed in clinical ovarian cancer specimens and cell lines using miRNA qRTPCR. The function of miR-124 on cell migration and invasion was confirmed in vitro through wound healing assay and transwell assay. Luciferase reporter assay was used to confirm target associations. RESULTS: We showed that miR-124 is down-regulated in ovarian cancer specimens as well as in cell lines; and that low-level expression of miR-124 is much lower in highly metastatic ovarian cancer cells and tissues. Meantime, overexpression of miR-124 dramatically inhibits the motility of ovarian cancer cells in vitro and substantially suppresses the protein expression of SphK1, reported as an invasion and metastasis-related gene in human cancers, whose expression is markedly increased in both ovarian cancer cell lines and clinical samples, particularly in two highly metastasis cells, SKOV3-ip and HO8910pm as well as metastatic ovarian tumor tissues. Furthermore, SphK1 is identified as a direct target of miR-124, and knock-down of SphK1 in ovarian cancer cells, SKOV3-ip and HO8910pm, could mimic the inhibition of migration and invasion by miR-124, while re-introduction of SphK1 abrogates the suppression of motility and invasiveness induced by miR-124 in both cell lines. CONCLUSIONS: Our studies suggest a protective role of miR-124 in inhibition of migration and invasion in the molecular etiology of ovarian cancer, and a potentially novel application of miR-124 in the regulation of migration and invasion in EOC.
| S-EPMC3879084 | biostudies-other
Project description:DEP Domain Containing 7 (DEPDC7) is highly and specifically expressed in normal liver tissue, belonging to the class of genes of liver-selective cell communication. Although the function of DEPDC7 remains poorly understood, its expression is decreased in liver cancer compared with normal liver tissues. It has previously been demonstrated that knockdown of DEPDC7 promotes cell growth, S phase entry and cell mobility and invasion in HepG2 cells. In the present study, it was shown that DEPDC7 expression is downregulated in four hepatoma cell lines (SMMC-7721, Huh-7, SK-Hep-1 and HepG2) and 48 hepatoma tissues, determined using western blot and immunohistochemical analysis. When DEPDC7 is overexpressed in hepatoma cell lines (SK-Hep-1 and Huh-7), it inhibits cell proliferation and cell growth; inhibits cell cycle entry; and inhibits cell motility and invasion. These results, together with the results of knockdown experiments, demonstrate that DEPDC7 may have an important role in hepatoma cells growth and metastasis and suggest it could be a therapeutic target; however, in vitro studies are required to validate this hypothesis.
| S-EPMC5755016 | biostudies-literature
Project description:Protein tyrosine kinase 6 (PTK6) has shown important cancer‑promoting effects in a variety of cancer types. Nonetheless, its vital role in cervical cancer has not been completely elucidated. The present study sought to address whether PTK6 is involved in the malignant progression of cervical cancer via its interaction with GRB2‑associated binding 1 (GAB1). Western blotting was used to examine PTK6 and GAB1 expression levels. Cell Counting Kit‑8, Transwell, wound healing, and terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labeling assays were performed to estimate the corresponding proliferative, migratory, invasive, and apoptotic abilities of the cells. Co‑immunoprecipitation (Co‑IP) assays confirmed binding of PTK6 to GAB1. The results revealed that the expression levels of PTK6 and GAB1 were markedly increased in cervical cancer cell lines compared with those noted in normal cervical epithelial cells. The cell proliferative, invasive, and migratory activities of cervical cancer cells were reduced in the absence of PTK6 expression, whereas the induction of apoptosis was aggravated under these conditions. The results of the Co‑IP assay indicated that PTK6 expression was positively associated with GAB1. In addition, the suppressive effect of PTK6 silencing on the malignant phenotypes of cervical cancer cells was reversed following overexpression of GAB1. In summary, the present study indicated that knockdown of PTK6 expression protected against the malignant progression of cervical cancer, while overexpression of GAB1 counteracted the inhibitory effects of PTK6 knockdown on cervical cancer cells.
| S-EPMC9366152 | biostudies-literature