MiR-374b-5p-FOXP1 feedback loop regulates cell migration, epithelial-mesenchymal transition and chemosensitivity in ovarian cancer

Background. Keratin 23 (KRT23) is a new member of the KRT gene family and known to be involved in the development and migration of various types of tumors. However, the role of KRT23 in ovarian cancer (OC) remains unclear. This study is aimed at investigating the function of KRT23 in OC. Methods. The expression of KRT23 in normal ovarian and OC tissues was determined using the Oncomine database and immunohistochemical staining. Reverse transcription quantitative polymerase chain reaction assay was used to analyze the expression of KRT23 in normal ovarian epithelial cell lines and OC cell lines. Small interfering RNA (siRNA), wound healing assay, and transwell assay were conducted to detect the effects of KRT23 on OC cell migration and invasion. Further mechanistic studies were verified by the Gene Expression Profiling Interactive Analysis platform, Western blotting, and immunofluorescence staining. Results. KRT23 was highly expressed in OC tissues and cell lines. High KRT23 expression could regulate OC cell migration and invasion, and the reduction of KRT23 by siRNA inhibited the migration and invasion of OC cells in vitro. Furthermore, KRT23 mediated epithelial-mesenchymal transition (EMT) by regulating p-Smad2/3 levels in the TGF-β/Smad signaling pathway. Conclusions. These results demonstrate that KRT23 plays an important role in OC migration via EMT by regulating the TGF-β/Smad signaling pathway.

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Involvement of Wnt/β-catenin pathway in the inhibition of invasion and epithelial-mesenchymal transition in ovarian cancer cells

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v19i7.4 ◽

2020 ◽

Vol 19 (7) ◽

pp. 1365-1370

Author(s):

Belikiz Ekem ◽

Wei Gong ◽

Lu Han ◽

Xinmei Wang ◽

Na Liu ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cell Migration ◽

Protein Expression ◽

Signaling Pathway ◽

Cell Invasion ◽

Epithelial Mesenchymal Transition ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Expression Levels

Purpose: To investigate the effects of zerumbone on cell invasion, epithelial-mesenchymal transition (EMT) and the potential signaling pathway involved in ovarian cancer cells.Methods: Caov-3 cell proliferation was assessed using 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide (MTT) assay. Wound healing assay was used to determine Caov-3 cell migration while cell invasion was evaluated using Transwell assay. Protein expression was determinedby western blot.Results: Cell viability was reduced by 5, 10, 20, and 50 μM zerumbone (p < 0.05) in a concentrationdependent manner while cell migration and invasion were inhibited by 10 and 20 μM zerumbone (p < 0.05). Protein expression levels of E-cadherin and cytoplasm β-catenin were upregulated by zerumbone (p < 0.05) in a concentration-dependent manner. On the other hand, protein expression levels of Ncadherin, vimentin, ZEB1, nuclear β-catenin, and c-Myc were suppressed by zerumbone (p < 0.05) also in a concentration-dependent manner.Conclusion: The results demonstrate that zerumbone inhibits cell proliferation, migration and invasion, but represses the EMT process via inactivation of Wnt/β-catenin signaling pathway. Keywords: Zerumbone, Ovarian cancer, Wnt/β-catenin pathway, Epithelial-mesenchymal transition

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Tumor-associated macrophages induced spheroid formation by CCL18-ZEB1-M-CSF feedback loop to promote transcoelomic metastasis of ovarian cancer

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-003973 ◽

2021 ◽

Vol 9 (12) ◽

pp. e003973

Author(s):

Lingli Long ◽

Yue Hu ◽

Tengfei Long ◽

Xiaofang Lu ◽

Ying Tuo ◽

...

Keyword(s):

Ovarian Cancer ◽

Feedback Loop ◽

Epithelial Mesenchymal Transition ◽

Three Dimensional ◽

Tumor Associated Macrophages ◽

Mesenchymal Transition ◽

Migration Assay ◽

Reverse Transcription Pcr ◽

Coculture System ◽

Specific Feedback

BackgroundOvarian cancer (OvCa)-tumor-associated macrophages (TAMs) spheroids are abundantly present within ascites of high malignant patients. This study investigated the mutual interaction of OvCa cells and TAMs in the spheroids.MethodsThree-dimensional coculture system and transwell coculture system were created to mimic the OvCa and TAMs in spheroids and in disassociated state. Transwell-migration assay and scratch wound healing assay were used to measure the invasive and migratory capacity. Western blot, quantitative reverse transcription-PCR and immunostaining were used to measure the mesenchymal and epithelial markers. Flow cytometry was used to assess the polarization of TAMs. Also, the differential gene expression profile of OvCa cells and OvCa cells from spheroids were tested by RNA-sequence. Finally, the ovarian mice models were constructed by intraperitoneal injection of ID8 or OvCa-TAMs spheroids.ResultsOur results indicated that the formation of OvCa-TAMs spheroids was positive related to the malignancy of OvCa cells. M2-TAMs induced the epithelial-mesenchymal transition of OvCa cells by releasing chemokine (C-C motif) ligand 18 (CCL18) in the spheroids. While, CCL18 induced macrophage colony-stimulating factor (M-CSF) transcription in OvCa cells through zinc finger E-box-binding homeobox 1 (ZEB1). This study further indicated that M-CSF secreted by OvCa cells drived the polarization of M2-TAMs. Therefore, a CCL18-ZEB1-M-CSF interacting loop between OvCa cells and TAMs in the spheroids was identified. Moreover, with blocking the expression of ZEB1 in the OvCa cell, the formation of OvCa-TAMs spheroids was impeded. In the ovarian mice models, the formation of OvCa-TAMs spheroids in the ascites was promoted by overexpressing of ZEB1 in OvCa cells, which resulted in faster and earlier transcoelomic metastasis.ConclusionThese findings suggested that the formation of OvCa-TAMs spheroids resulted in aggressive phenotype of OvCa cells, as a specific feedback loop CCL18-ZEB1-M-CSF in it. Inhibition of ZEB1 reduced OvCa-TAMs spheroids in the ascites, impeding the transcoelomic metastasis and improving the outcome of ovarian patients.

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LncRNA SRA mediates cell migration, invasion, and progression of ovarian cancer via NOTCH signaling and epithelial-mesenchymal transition

Bioscience Reports ◽

10.1042/bsr20210565 ◽

2021 ◽

Author(s):

Lee Kyung Kim ◽

Sun-Ae Park ◽

Yoolhee Yang ◽

Young Tae Kim ◽

Tae-Hwe Heo ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Migration ◽

Cancer Patients ◽

Epithelial Mesenchymal Transition ◽

Gynecological Cancer ◽

Notch Pathway ◽

Tumor Formation ◽

High Expression ◽

Free Survival ◽

Mesenchymal Transition

Long non-coding RNA (lncRNA) is a newly identified regulator of tumor formation and tumor progression. The function and expression of lncRNAs remain to be fully elucidated, but recent studies have begun to address their importance in human health and disease. The lncRNA, SRA, known as Steroid receptor activator, acts as an important modulator of gynecological cancer, and its expression may affect biological functions including proliferation, apoptosis, steroid formation and muscle developments. However, it is still not well known whether SRA is involved in the regulation of ovarian cancer. This study investigated the molecular function and association between SRA expression and clinicopathological factors. In ovarian cancer cell lines, SRA knockdown and overexpression regulated cell migration, proliferation, and invasion. Both in vivo and in vitro experiments using knockdown and overexpression showed that SRA potently regulated epithelial-mesenchymal transition and NOTCH pathway components. Further, clinical data confirmed that SRA was a significant predictor of overall survival and progression-free survival and patients with ovarian cancer exhibiting high expression of SRA exhibited higher recurrence rates than patients with low SRA expression. In conclusion, this study indicates that SRA has clinical significance as its expression can predict the prognosis of ovarian cancer patients. High expression of the lncRNA SRA is strongly correlated with recurrence-free survival of ovarian cancer patients.

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