KIAA1199 induces advanced biological behavior and development of ovarian cancer through activation of the IL-6/STAT3 pathway

Abstract Objectives: The purpose of this study was to investigate the expression and clinical significance of LncRNA OIP5-AS1 in ovarian cancer , as well as its effect on malignant biological behavior of ovarian cancer cells. Methods: The expression of OIP5-AS1, miR-153-3p and KLF5 in ovarian cancer (OC) tissues and cells were detected by RT-qPCR. Western Blotting was used to detect KLF5 expression. The expression patterns of OIP5-AS1, U6 and GAPDH in nuclear and cytoplasm fractions were detected using qRT-PCR. Besides, CCK-8 assay, clone formation assay, transwell, scratch test, and flow cytometry were respectively used to detect the cell activity, proliferation, invasiveness, healing of cells, and apoptosis rate of OC cells. Furthermore, The interaction between OIP5-AS1 and miR-153-3p and between miR-153-3p and KLF5 were verified by luciferase reporter assay, and the correlations among these three genes were analyzed.Results: OIP5-AS1 expression was up-regulated in ovarian cancer cell lines and tissues. Si-OIP5-AS1 inhibited cell proliferation, invasion and migration, and induced the apoptosis to a certain extent. Subcellular fraction assay revealed the location of OIP5-AS1 was mainly situated in the cytoplasm. In addition, miR-153-3p was a target of OIP5-AS1, and KLF5 was directly targeted by miR-153-3p. Si-OIP5-AS1 inhibited KLF5 expression, miR-153-3p inhibitor promoted KLF5 expression, and si-KLF5 inhibited OIP5-AS1 expression. Interestingly, expression of OIP5-AS1 and miR-153-3p, and expression of miR-153-3p and KLF5 were negatively correlated, while expression of OIP5-AS1 and KLF5 was positively correlated. In addition, si-KLF5 inhibited the malignant biological behavior of ovarian cancer cells, while miR-153-3p inhibitor had the opposite effect. Most importantly, the addition of si-OIP5-AS1 to mir-153-3p silenced cells could reverse the promotion effect of miR-153-3p inhibitor on the malignant biological behavior of ovarian cancer cells.Conclusions: OIP5-AS1 can be used as an effective prognostic indicator of ovarian cancer, which has the potential to be a new drug target.

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Identification of PKP 2/3 as potential biomarkers of ovarian cancer based on bioinformatics and experiments

Cancer Cell International ◽

10.1186/s12935-020-01602-3 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Lingling Gao ◽

Xiao Li ◽

Qian Guo ◽

Xin Nie ◽

Yingying Hao ◽

...

Keyword(s):

Ovarian Cancer ◽

Signaling Pathway ◽

Poor Prognosis ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Biological Behavior ◽

Cell Junction ◽

Immune Infiltration ◽

Potential Biomarker

Abstract Background Plakophilins (PKPs) are widely involved in gene transcription, translation, and signal transduction, playing a crucial role in tumorigenesis and progression. However, the function and potential mechanism of PKP1/2/3 in ovarian cancer (OC) remains unclear. It’s of great value to explore the expression and prognostic values of PKP1/2/3 and their potential mechanisms, immune infiltration in OC. Methods The expression levels, prognostic values and genetic variations of PKP1/2/3 in OC were explored by various bioinformatics tools and databases, and PKP2/3 were selected for further analyzing their regulation network and immune infiltration. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathways (KEGG) enrichment were also conducted. Finally, the expression and prognosis of PKP2 were validated by immunohistochemistry. Results The expression level and prognosis of PKP1 showed little significance in ovarian cancer, and the expression of PKP2/3 mRNA and protein were upregulated in OC, showing significant correlations with poor prognosis of OC. Functional enrichment analysis showed that PKP2/3 and their correlated genes were significantly enriched in adaptive immune response, cytokine receptor activity, organization of cell–cell junction and extracellular matrix; KEGG analysis showed that PKP2/3 and their significantly correlated genes were involved in signaling pathways including cytokine-mediated signaling pathway, receptor signaling pathway and pathways in cancer. Moreover, PKP2/3 were correlated with lymphocytes and immunomodulators. We confirmed that high expression of PKP2 was significantly associated with advanced stage, poor differentiation and poor prognosis of OC patients. Conclusion Members of plakophilins family showed various degrees of abnormal expressions and prognostic values in ovarian cancer. PKP2/3 played crucial roles in tumorigenesis, aggressiveness, malignant biological behavior and immune infiltration of OC, and can be regarded as potential biomarker for early diagnosis and prognosis evaluation in OC.

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Alternatively activated macrophage-derived secretome stimulates ovarian cancer spheroid spreading through a JAK2/STAT3 pathway

Cancer Letters ◽

10.1016/j.canlet.2019.05.029 ◽

2019 ◽

Vol 458 ◽

pp. 92-101 ◽

Cited By ~ 6

Author(s):

Kaitlin C. Fogg ◽

Will R. Olson ◽

Jamison N. Miller ◽

Aisha Khan ◽

Carine Renner ◽

...

Keyword(s):

Ovarian Cancer ◽

Stat3 Pathway ◽

Activated Macrophage ◽

Alternatively Activated Macrophage ◽

Alternatively Activated

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Early responses of the STAT3 pathway to platinum drugs are associated with cisplatin resistance in epithelial ovarian cancer

Brazilian Journal of Medical and Biological Research ◽

10.1590/1414-431x20133003 ◽

2013 ◽

Vol 46 (8) ◽

pp. 650-658 ◽

Cited By ~ 20

Author(s):

W.J. Sheng ◽

H. Jiang ◽

D.L. Wu ◽

J.H. Zheng

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Cisplatin Resistance ◽

Platinum Drugs ◽

Stat3 Pathway

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An Advanced Orthotopic Ovarian Cancer Model in Mice for Therapeutic Trials

BioMed Research International ◽

10.1155/2016/2585787 ◽

2016 ◽

Vol 2016 ◽

pp. 1-4 ◽

Cited By ~ 2

Author(s):

Ying Zhang ◽

Li Luo ◽

Xueling Zheng ◽

Tinghe Yu

Keyword(s):

Ovarian Cancer ◽

Survival Time ◽

Biological Behavior ◽

In Vivo Model ◽

Ovarian Cancer Cells ◽

Recipient Mouse ◽

Cancer Model ◽

Therapeutic Trials ◽

Tumor Fragment

A nude mouse received subcutaneous injection of human ovarian cancer cells HO-8910PM to form a tumor, and then the tumor fragment was surgically transplanted to the ovary of a recipient mouse to establish an orthotopic cancer model. Tumors occurred in 100% of animals. A mouse displayed an ovarian mass, ascites, intraperitoneal spread, and lung metastasis at natural death. The mean survival time was34.1±17.2days, with median survival time of 28.5 days. The findings indicated that the present mouse model can reflect the biological behavior of advanced human ovarian cancers. This in vivo model can be used to explore therapeutic means against chemoresistance and metastasis, and an effective treatment would prolong the survival time.

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Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway

Toxicology and Applied Pharmacology ◽

10.1016/j.taap.2011.10.009 ◽

2012 ◽

Vol 258 (1) ◽

pp. 72-81 ◽

Cited By ~ 121

Author(s):

Miran Jo ◽

Mi Hee Park ◽

Pushpa Saranya Kollipara ◽

Byeong Jun An ◽

Ho Sueb Song ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Death Receptors ◽

Bee Venom ◽

Ovarian Cancer Cells ◽

Stat3 Pathway ◽

Venom Toxin ◽

Anti Cancer

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Inhibition of the JAK2/STAT3 pathway in ovarian cancer results in the loss of cancer stem cell-like characteristics and a reduced tumor burden

BMC Cancer ◽

10.1186/1471-2407-14-317 ◽

2014 ◽

Vol 14 (1) ◽

Cited By ~ 68

Author(s):

Khalid Abubaker ◽

Rodney B Luwor ◽

Hongjian Zhu ◽

Orla McNally ◽

Michael A Quinn ◽

...

Keyword(s):

Ovarian Cancer ◽

Stem Cell ◽

Cancer Stem Cell ◽

Tumor Burden ◽

Stat3 Pathway

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The inhibitory effect of curcumin via fascin suppression through JAK/STAT3 pathway on metastasis and recurrence of ovary cancer cells.

10.21203/rs.3.rs-40272/v3 ◽

2020 ◽

Author(s):

Mi Ju Kim

Keyword(s):

Ovarian Cancer ◽

Cell Viability ◽

Anticancer Activity ◽

Cancer Cells ◽

Short Exposure ◽

Ovarian Cancer Cells ◽

Invasion Assay ◽

Stat3 Pathway ◽

Migration Assay ◽

Ovary Cancer

Abstract Background: fascin is an actin-binding protein and highly expressed in ovarian cancer cells. It is associated with metastasis of cancer and may be a useful prognostic factor. Anticancer activity of curcumin is related to its effect on several signaling mechanisms. Although there have been many reports regarding the anticancer properties of curcumin, its inhibitory effects on migration and invasion of ovarian cancer cells, particularly in the context of fascin expression, have not been reported. The purpose of this study was to investigate the effect of curcumin on fascin expression in ovarian cancer cells and to propose a possible mechanism for the anticancer activity of curcumin through reduced fascin expression. Methods: SKOV3, human epithelial ovary cancer cell line, was cultured with curcumin at various dose and duration. The fascin was quantified using cell viability test and Western blot. To determine the effect of curcumin on the upstream pathway of fascin expression, the signal transducer and activator of transcription 3 (STAT3) was analyzed by sandwich-ELISA. Attachment assay, migration assay and invasion assay were analyzed to approve the change of cellular invasiveness of ovary cancer after curcumin. To determine the morphological changes of ovarian cancer cells by curcumin, immunofluorescence was performed. Results: MTS assays showed that cell viability was different at various concentration of curcumin, and as concentration increased, cell viability tended to decrease. Curcumin appears to suppress fascin expression, even with a minimal concentration and short exposure time. Also, curcumin may suppress fascin expression in ovarian cancer cells through STAT3 downregulation. The attachment assay, migration assay and invasion assay of the ovarian cancer cells exhibited a statistically significant decrease. Immunofluorescence revealed a change of cell shape from a typical form of uninfluenced cells to a more polygonal appearance, with a significant reduction in filopodia formation. Conclusions: Curcumin reduces fascin expression through JAK/STAT3 pathway inhibition, which interferes with the cellular interactions essential for the metastasis and recurrence of ovarian cancer cells. Higher curcumin concentrations and longer exposure times concomitantly decreased fascin expression.

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Knockdown of HE4 suppresses aggressive cell growth and malignant progression of ovarian cancer by inhibiting the JAK/STAT3 pathway

Biology Open ◽

10.1242/bio.043570 ◽

2019 ◽

Vol 8 (9) ◽

pp. bio043570 ◽

Cited By ~ 1

Author(s):

Aihong Wang ◽

Canhui Jin ◽

Xiaoyu Tian ◽

Ying Wang ◽

Hongyu Li

Keyword(s):

Ovarian Cancer ◽

Cell Growth ◽

Malignant Progression ◽

Stat3 Pathway

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Overexpression of BMPER in Ovarian Cancer and the Mechanism by which It Promotes Malignant Biological Behavior in Tumor Cells

BioMed Research International ◽

10.1155/2020/3607436 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Yong Xi ◽

Xin Nie ◽

Jing Wang ◽

Lingling Gao ◽

Bei Lin

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Tumor Cells ◽

Poor Prognosis ◽

Malignant Tumors ◽

Biological Behavior ◽

Ovarian Cancer Cells ◽

Epithelial Tumor ◽

Tumor Tissues ◽

Ovarian Epithelial Tumor

Background. BMPER has been reported to be associated with the biological behavior of a few malignant tumors, but the mechanism is still unclear. We aimed to detect BMPER expression in ovarian epithelial tumor tissues and its effects on their biological behaviors, as well as to elucidate the possible mechanism. Methods. BMPER expression in ovarian epithelial tumor tissues was detected by immunohistochemistry. BMPER expression in ovarian cancer cell lines was inhibited via RNA interference. Changes in the malignant behaviors of ovarian cancer cells were detected by MTT, wound healing, Transwell, and flow cytometry assays. Changes in proteins in the MAPK and autophagy-related signaling pathways were detected by Western blot analysis. Results. The expression of BMPER was significantly upregulated in ovarian epithelial malignant tumors and was related to increased lymph node metastasis and lower survival rate. High BMPER expression is an independent risk factor for poor prognosis in patients. Inhibition of BMPER inhibited the proliferation, invasion, and migration of ovarian cancer cells and promoted apoptosis. In addition, BMPER downregulation decreased the expression of PCNA, Bcl-2, MMP2, and MMP9 and increased the expression of Bax. Moreover, the levels of p-ERK, p-MEK, and the autophagy-related protein p-mTOR were decreased, and Beclin 1 levels and the LC3II/I ratio were increased. Conclusions. Our findings indicated that BMPER is closely related to poor prognosis in ovarian cancer. BMPER plays a role in promoting the malignant biological behavior of tumor cells through the MAPK and autophagy-related signaling pathways.

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