scholarly journals Overexpression of NPTX2 Promotes Malignant Phenotype of Epithelial Ovarian Carcinoma via IL6-JAK2/STAT3 Signaling Pathway Under Hypoxia

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaotian Han ◽  
Yechen Lu ◽  
Xiaoqi Li ◽  
Lingfang Xia ◽  
Hao Wen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Signaling Pathway ◽  
Western Blotting ◽  
Poor Prognosis ◽  
Molecular Therapy ◽  
Luciferase Reporter ◽  
Malignant Phenotype ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Neuronal Pentraxin

BackgroundEpithelial ovarian cancer (EOC) is the main subtype of ovarian cancer and shows an aggressive phenotype and poor prognosis. Neuronal pentraxin II (NPTX2) is a member of the neuronal pentraxin family and plays a contradictory role in different tumors. However, there has been no report about the possible role and effect of NPTX2 in EOC.MethodsBioinformatics analysis, qPCR, western blotting and immunohistochemistry were used to detect the expression of NPTX2 in EOC. Lentivirus-based transfection for NPTX2 overexpression or knockdown was performed on the EOC cell lines A2780, HEY, SKOV3 and OVCAR-3. The effect of NPTX2 on the malignant phenotype of EOC was examined through methods of MTS assay, Edu assay, transwell assay, western blotting analysis, qPCR analysis, luciferase reporter assay and xenograft experiment.ResultsEOC tissues showed higher NPTX2 expression than the normal tissues with poor prognosis. NPTX2 overexpression can promote the proliferation, invasion, migration and tumorigenesis of EOC via IL6-JAK2/STAT3 signaling pathway. Moreover, hypoxia-inducible factor-1(HIF-1) can promote the transcription and expression of NPTX2 under the hypoxic environment. NPTX2 knockdown abolished the hypoxia-induced malignant phenotypes in ECO.ConclusionsThe above results suggest that NPTX2 may play a novel role in ovarian cancer’s malignant phenotype and act as a promising treatment target for EOC molecular therapy.

scholarly journals Overexpression of NPTX2 Promotes Malignant Phenotypeof Epithelial Ovarian Carcinoma via IL6-JAK2/STAT3 Signaling Pathway Under Hypoxia

2020 ◽  
Author(s):  
Xiaotian Han ◽  
Yechen Lu ◽  
Xiaoqi Li ◽  
Lingfang Xia ◽  
Hao Wen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Signaling Pathway ◽  
Western Blotting ◽  
Poor Prognosis ◽  
Hypoxia Inducible Factor ◽  
Luciferase Reporter ◽  
Malignant Phenotype ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Neuronal Pentraxin

Abstract Background: Epithelial ovarian cancer(EOC) is the main subtype of ovarian cancer and shows an aggressive phenotype and poor prognosis. Neuronal pentraxin II (NPTX2)is a member of the neuronal pentraxin family and plays a contradictory role in different tumors. However, there has been no report about the possible role and effect of NPTX2 in EOC.Methods: Bioinformatics analysis, qPCR, western blotting and immunohistochemistry were used to detect the expression of NPTX2 in EOC. Lentivirus-based transfection for NPTX2 overexpression or knockdown was performed on the EOC cell lines A2780, HEY, SKOV3 and OVCAR-3. The effect of NPTX2 on the malignant phenotype of EOC was examined through methods of MTS assay, Edu assay, transwell assay, western blotting analysis, qPCR analysis, luciferase reporter assay and xenograft experiment.Results: EOC tissues showed higher NPTX2 expression than the normal tissues with poor prognosis. NPTX2 overexpression can promote the proliferation, invasion, migration and tumorigenesis of EOC via IL6-JAK2/STAT3 signaling pathway. Moreover, hypoxia-inducible factor-1(HIF-1) can promote the transcription and expression of NPTX2 under the hypoxic environment.Conclusions: The above results suggest that NPTX2 may play a novel role in ovarian cancer's malignant phenotype and act asa promising treatment target for EOC moleculartherapy.

scholarly journals Krupple-Like Factor 5 is a Potential Therapeutic Target and Prognostic Marker in Epithelial Ovarian Cancer

2020 ◽  
Vol 11 ◽  
Author(s):  
Abdul K. Siraj ◽  
Poyil Pratheeshkumar ◽  
Sasidharan Padmaja Divya ◽  
Sandeep Kumar Parvathareddy ◽  
Khadija A. Alobaisi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Growth ◽  
Epithelial Ovarian Cancer ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Therapeutic Target ◽  
Potential Therapeutic Target ◽  
Mesenchymal Transition ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy. Despite current therapeutic and surgical options, advanced EOC shows poor prognosis. Identifying novel molecular therapeutic targets is highly needed in the management of EOC. Krupple-like factor 5 (KLF5), a zinc-finger transcriptional factor, is highly expressed in a variety of cancer types. However, its role and expression in EOC is not fully illustrated. Immunohistochemical analysis was performed to assess KLF5 protein expression in 425 primary EOC samples using tissue microarray. We also addressed the function of KLF5 in EOC and its interaction with signal transducer and activator of transcription 3 (STAT3) signaling pathway. We found that KLF5 overexpressed in 53% (229/425) of EOC samples, and is associated with aggressive markers. Forced expression of KLF5 enhanced cell growth in low expressing EOC cell line, MDAH2774. Conversely, knockdown of KLF5 reduced cell growth, migration, invasion and progression of epithelial to mesenchymal transition in KLF5 expressing cell lines, OVISE and OVSAHO. Importantly, silencing of KLF5 decreased the self-renewal ability of spheroids generated from OVISE and OVSAHO cell lines. In addition, downregulation of KLF5 potentiated the effect of cisplatin to induce apoptosis in these cell lines. These data reveals the pro-tumorigenic role of KLF5 in EOC and uncover its role in activation of STAT3 signaling pathway, suggesting the importance of KLF5 as a potential therapeutic target for EOC therapy.

scholarly journals ALKBH5-HOXA10 loop-mediated JAK2 m6A demethylation and cisplatin resistance in epithelial ovarian cancer

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Sipei Nie ◽  
Lin Zhang ◽  
Jinhui Liu ◽  
Yicong Wan ◽  
Yi Jiang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Signaling Pathway ◽  
Cisplatin Resistance ◽  
Rna Seq ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Rna Immunoprecipitation

Abstract Background Chemotherapy resistance remains a barrier to improving the prognosis of epithelial ovarian cancer (EOC). ALKBH5 has recently been shown to be one of the RNA N6-methyladenosine (m6A) demethyltransferases associated with various cancers, but its role in cancer therapeutic resistance remains unclear. This study aimed to investigate the role of AlkB homolog 5 (ALKBH5) in cisplatin-resistant EOC. Methods Functional assays were performed both in vitro and in vivo. RNA sequencing (RNA-seq), m6A-modified RNA immunoprecipitation sequencing (MeRIP-seq), chromatin immunoprecipitation, RNA immunoprecipitation, and luciferase reporter and actinomycin-D assays were performed to investigate RNA/RNA interaction and m6A modification of the ALKBH5-HOXA10 loop. Results ALKBH5 was upregulated in cisplatin-resistant EOC and promoted cancer cell cisplatin resistance both in vivo and in vitro. Notably, HOXA10 formed a loop with ALKBH5 and was found to be the upstream transcription factor of ALKBH5. HOXA10 overexpression also facilitated EOC cell chemoresistance both in vivo and in vitro. Collective results of MeRIP-seq and RNA-seq showed that JAK2 is the m6A-modified gene targeted by ALKBH5. The JAK2/STAT3 signaling pathway was activated by overexpression of the ALKBH5-HOXA10 loop, resulting in EOC chemoresistance. Cell sensitivity to cisplatin was rescued by ALKBH5 and HOXA10 knockdown or inhibition of the JAK2/STAT3 signaling pathway in EOC cells overexpressing ALKBH5-HOXA10. Conclusions The ALKBH5-HOXA10 loop jointly activates the JAK2/STAT3 signaling pathway by mediating JAK2 m6A demethylation, promoting EOC resistance to cisplatin. Thus, inhibition of the expression of the ALKBH5-HOXA10 loop may be a potential strategy to overcome cisplatin resistance in EOC.

scholarly journals LINC00893 Inhibits The Progression of Prostate Cancer Through miR-3173-5p/SOCS3/JAK2/STAT3 Pathway

2021 ◽  
Author(s):  
Chuigong Yu ◽  
Yu Fan ◽  
Yu Zhang ◽  
Lupeng Liu ◽  
Gang Guo
Keyword(s):  
Prostate Cancer ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Janus Kinase ◽  
Luciferase Reporter ◽  
Mesenchymal Transition ◽  
Stat3 Pathway ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

Abstract Background: Prostate cancer (PCa) is one of the most common malignant tumors in the male urinary system. In recent years, the morbidity and mortality of PCa have been increasing due to the limited effects of existing treatment strategies. Long non-coding RNA (lncRNA) LINC00893 inhibits the proliferation and metastasis of papillary thyroid cancer (PTC) cells, but its role in PCa has not been reported. Our study aims to clarify the role and underlying mechanism of LINC00893 in regulating the progression of PCa.Methods: We analyzed LINC00893 expression through TCGA database. We also collected 66 paires of PCa tissues and matched para-cancerous tissues as well as cell lines and assessed LINC00893 expression. Subsequently, we conducted gain-of-function assays to confirm the role of LINC00893 in PCa. CCK-8, EdU, colony information and transwell assays were implemented to detect cell proliferation, colony formation and metastasis abilities, respectively. RT-qPCR and western blot assays were used to quantify the expression of mRNA and protein. Dual-luciferase reporter, RNA-binding protein immunoprecipitation (RIP) and RNA pull down assays were conducted to evaluate the interaction of molecules. Spearman correlation coefficient analysis was conducted to detect the correlation between molecules.Results: We found that the LINC00893 expression in PCa tissues and cell lines was upregulated compared with matched controls, and patients with low expression of LINC00893 suffered a low overall survival rate. Overexpression of LINC00893 hindered the proliferation, epithelial-mesenchymal transition (EMT) as well as metastasis of PCa cells in vitro and in vivo. In terms of mechanism, suppressor of cytokine signaling 3 (SOCS3)/Janus Kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway occupied a central position in the regulation of PCa progression by LINC00893. LINC00893 weakened the inhibition role of miR-3173-5p on SOCS3 expression through functioning as a miR-3173-5p sponge, which inhibited the JAK2/STAT3 signaling pathway. Conclusions: LINC00893 suppresses the progression of prostate cancer through miR-3173-5p/SOCS3/JAK2/STAT3 pathway. our data uncovers a novel mechanism by which LINC00893 hinders the progression of PCa, which enriches the molecular network of LINC00893 regulating the PCa progression and laies a theoretical foundation for PCa targeted therapy.

scholarly journals MicroRNA-214 prevents pulmonary angiogenesis and alveolarization in neonatal rats with hyperoxia-mediated impairment of lung development by blocking PlGF-dependent STAT3 signaling pathway

2020 ◽  
Author(s):  
Zhi-Qun Zhang ◽  
Xiao-Xia Li ◽  
Jing Li ◽  
Hui Hong ◽  
Xian-Mei Huang
Keyword(s):  
Epithelial Cells ◽  
Signaling Pathway ◽  
Preterm Infants ◽  
Neonatal Rat ◽  
Luciferase Reporter ◽  
Neonatal Rats ◽  
Stat3 Signaling ◽  
Pulmonary Epithelial Cells ◽  
Stat3 Signaling Pathway ◽  
Gene Assay

AbstractIn recent years, the roles of microRNAs (miRNAs) in pulmonary diseases have been widely studied and researched. However, the molecular mechanism by which miR-214 affects bronchopulmonary dysplasia (BPD) remains elusive and merits further exploration. Hence, this study aims to clarify the function of miR-214 in pulmonary angiogenesis and alveolarization in preterm infants with BPD. BPD neonatal rat model was induced by hyperoxia, and pulmonary epithelial cells were isolated from rats and exposed to hyperoxia. Gain- or loss-of-function experiments were performed in BPD neonatal rats and hyperoxic pulmonary epithelial cells. MiR-214 and PlGF expression in BPD neonatal rats, and eNOS, Bcl-2, c-myc, Survivin, α-SMA and E-cadherin expression in hyperoxic pulmonary epithelial cells were detected using RT-qPCR and western blot analysis. The interaction between PlGF and miR-214 was identified using dual luciferase reporter gene assay and RIP assay. ELISA was adopted to assess IL-1β, TNF-a, IL-6, ICAM-1 and Flt-1 expression in rats. Decreased miR-214 expression and elevated PlGF expression were evident in the lung tissues of neonatal rats with BPD. PlGF was a target of miR-214, and miR-214 downregulated PlGF to inactivate the STAT3 signaling pathway. miR-214 overexpression or PlGF silencing decreased apoptosis of hyperoxic pulmonary epithelial cells and declined pulmonary angiogenesis and alveolarization in BPD neonatal rats. Collectively, miR-214 can protects against pulmonary angiogenesis and alveolarization in preterm infants with BPD by suppressing PlGF and blocking STAT3 signaling pathway.

scholarly journals ALKBH5-HOXA10 loop-mediated JAK2 m6A demethylation and platinum resistance in epithelial ovarian cancer

2021 ◽  
Author(s):  
Sipei Nie ◽  
Lin Zhang ◽  
Jinhui Liu ◽  
Yicong Wan ◽  
Yi Jiang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Signaling Pathway ◽  
Platinum Resistance ◽  
Rna Seq ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Rna Immunoprecipitation

Abstract Background: Chemotherapy resistance remains a barrier in improving the prognosis of epithelial ovarian cancer (EOC), but its mechanism remains to be elucidated. ALKBH5 has been recently proven to be an RNA N6-methyladenosine (m6A) demethyltransferase associated with various cancers, but its role in cancer therapeutic resistance remains unclear. This study aimed to investigate the role of AlkB homolog 5 (ALKBH5) in platinum-resistant EOC.Methods: Functional assays were performed both in vitro and in vivo. RNA sequencing (RNA-seq), m6A-modified RNA immunoprecipitation sequencing (MeRIP-seq), chromatin immunoprecipitation, RNA immunoprecipitation, and luciferase reporter and actinomycin-D assays were performed to investigate RNA/RNA interaction and m6A modification of the ALKBH5-HOXA10 loop.Results: ALKBH5 was upregulated in platinum-resistant EOC and promoted cancer cell cisplatin resistance both in vivo and in vitro. Notably, HOXA10 was found to be the upstream transcription factor of ALKBH5 and formed a loop with ALKBH5., and its overexpression facilitated EOC cell chemoresistance both in vivo and in vitro. HOXA10 overexpression was found to facilitate EOC cell chemoresistance both in vivo and in vitro. Collective results of MeRIP-seq and RNA-seq showed that JAK2 is an m6A-modified gene targeted by ALKBH5. The JAK2/STAT3 signaling pathway was activated by overexpression of the ALKBH5-HOXA10 loop, and this resulted in EOC chemoresistance. Cell sensitivity to cisplatin was rescued by ALKBH5 and HOXA10 knockdown or inhibition of the JAK2/STAT3 signaling pathway in EOC cells overexpressing ALKBH5-HOXA10.Conclusions: The ALKBH5-HOXA10 loop jointly activates the JAK2/STAT3 signaling pathway by mediating JAK2 m6A demethylation, promoting EOC resistance to platinum. Thus, inhibition of the expression of the ALKBH5-HOXA10 loop maybe a potential strategy to overcome platinum resistance in EOC.

scholarly journals SPTBN1 suppresses the progression of epithelial ovarian cancer via SOCS3-mediated blockade of the JAK/STAT3 signaling pathway

Aging ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 10896-10911
Author(s):  
Mo Chen ◽  
Jia Zeng ◽  
Shuyi Chen ◽  
Jiajia Li ◽  
Huijie Wu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Signaling Pathway ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway
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