scholarly journals CircRNA hsa_circ_0013958 may contribute to the development of ovarian cancer by affecting epithelial‐mesenchymal transition and apoptotic signaling pathways

2020 ◽  
Vol 34 (7) ◽  
Author(s):  
Cheng Pei ◽  
Han Wang ◽  
Cong Shi ◽  
Chuanqi Zhang ◽  
Min Wang
Keyword(s):  
Ovarian Cancer ◽  
Signaling Pathways ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Apoptotic Signaling

scholarly journals Ovarian Cancer and Cancer Stem Cells—Cellular and Molecular Characteristics, Signaling Pathways, and Usefulness as a Diagnostic Tool in Medicine and Oncology

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4178
Author(s):  
Andrzej Nowicki ◽  
Magdalena Kulus ◽  
Maria Wieczorkiewicz ◽  
Wojciech Pieńkowski ◽  
Katarzyna Stefańska ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Signaling Pathways ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Development ◽  
Molecular Characteristics ◽  
Mesenchymal Transition

Despite the increasing development of medicine, ovarian cancer is still a high-risk, metastatic disease that is often diagnosed at a late stage. In addition, difficulties in its treatment are associated with high resistance to chemotherapy and frequent relapse. Cancer stem cells (CSCs), recently attracting significant scientific interest, are considered to be responsible for the malignant features of tumors. CSCs, as the driving force behind tumor development, generate new cells by modifying different signaling pathways. Moreover, investigations on different types of tumors have shown that signaling pathways are key to epithelial-mesenchymal transition (EMT) regulation, metastasis, and self-renewal of CSCs. Based on these established issues, new therapies are being investigated based on the use of inhibitors to block CSC growth and proliferation signals. Many reports indicate that CSC markers play a key role in cancer metastasis, with hopes placed in their targeting to block this process and eliminate relapses. Current histological classification of ovarian tumors, their epidemiology, and the most recent knowledge of ovarian CSCs, with particular emphasis on their molecular background, are important aspects for consideration. Furthermore, the importance of signaling pathways involved in tumor growth, development, and metastasis, is also presented.

Upregulation of Bromodomain PHD‑finger transcription factor in ovarian cancer and its critical role for cancer cell proliferation and survival

2020 ◽  
Author(s):  
Juan Miao ◽  
Min Zhang ◽  
Xiaohao Huang ◽  
Lei Xu ◽  
Ranran Tang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Transcription Factor ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Nucleosome Remodeling ◽  
Phd Finger ◽  
Mesenchymal Transition

Abstract: Bromodomain PHD finger transcription factor (BPTF) is a core subunit of nucleosome-remodeling factor (NURF) complex, which plays an important role in the development of several cancers. However, it is unknown whether BPTF regulates ovarian cancer (OC) progression. Relative expression of BPTF in cell lines and tissues of OC were measured by Western blot and immunohistochemistry respectively. Clinical significance of BPTF in OC was analyzed by Chisquare test. BPTF knockdown effects on the proliferation, migration, invasion and apoptosis of OC cells were examined. Mechanism studies revealed that these effects were achieved through simultaneous modulation of multiple signaling pathways. We found that BPTF was highly expressed in OC cell lines and tissues compared with normal human ovarian epithelial cell and non-cancerous tissues (p<0.05). These results are also supported by the public RNA-seq data. BPTF overexpression was correlated with poor ovarian cancer patient survival (p<0.05). Vitro experiments revealed that the down-regulation of BPTF inhibited OC cell proliferation, colony formation, migration, invasion and induced its apoptosis. BPTF knockdown also regulated the epithelial-mesenchymal transition (EMT) signaling pathways and induced the cleavage of apoptosis-related proteins. Consequently, BPTF plays a critical role in regulating OC cell survival and functions as a potential therapeutic target for OC.

scholarly journals A novel homeostatic loop of sorcin drives paclitaxel-resistance and malignant progression via Smad4/ZEB1/miR-142-5p in human ovarian cancer

Oncogene ◽  
2021 ◽  
Author(s):  
Jinguo Zhang ◽  
Wencai Guan ◽  
Xiaolin Xu ◽  
Fanchen Wang ◽  
Xin Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Calcium Binding ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Progression ◽  
Bioinformatics Analyses ◽  
Aberrant Expression ◽  
Mesenchymal Transition ◽  
E Box

AbstractThe primary chemotherapy of ovarian cancer (OC) often acquires chemoresistance. Sorcin (SRI), a soluble resistance-related calcium-binding protein, has been reported to be an oncogenic protein in cancer. However, the molecular mechanisms of SRI regulation and the role and aberrant expression of SRI in chemoresistant OC remain unclear. Here, we identified SRI as a key driver of paclitaxel (PTX)-resistance and explored its regulatory mechanism. Using transcriptome profiles, qRT-PCR, proteomics, Western blot, immunohistochemistry, and bioinformatics analyses, we found that SRI was overexpressed in PTX-resistant OC cells and the overexpression of SRI was related to the poor prognosis of patients. SRI was a key molecule required for growth, migration, and PTX-resistance in vitro and in vivo and was involved in epithelial–mesenchymal transition (EMT) and stemness. Mechanistic studies showed that miR-142-5p directly bound to the 3ʹ-UTR of SRI to suppress its expression, whereas a transcription factor zinc-finger E-box binding homeobox 1 (ZEB1) inhibited the transcription of miR-142-5p by directly binding to the E-box fragment in the miR-142 promoter region. Furthermore, ZEB1 was negatively regulated by SRI which physically interacted with Smad4 to block its translocation from the cytosol to the nucleus. Taken together, our findings unveil a novel homeostatic loop of SRI that drives the PTX-resistance and malignant progression via Smad4/ZEB1/miR-142-5p in human OC. Targeting this SRI/Smad4/ZEB1/miR-142-5p loop may reverse the PTX-resistance.

scholarly journals The Epithelial–Mesenchymal Transcription Factor SNAI1 Represses Transcription of the Tumor Suppressor miRNA let-7 in Cancer

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1469
Author(s):  
Hanmin Wang ◽  
Evgeny Chirshev ◽  
Nozomi Hojo ◽  
Tise Suzuki ◽  
Antonella Bertucci ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cell ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Burden ◽  
Cell Phenotype ◽  
Mesenchymal Transition ◽  
Carcinoma Cell Lines ◽  
Future Work

We aimed to determine the mechanism of epithelial–mesenchymal transition (EMT)-induced stemness in cancer cells. Cancer relapse and metastasis are caused by rare stem-like cells within tumors. Studies of stem cell reprogramming have linked let-7 repression and acquisition of stemness with the EMT factor, SNAI1. The mechanisms for the loss of let-7 in cancer cells are incompletely understood. In four carcinoma cell lines from breast cancer, pancreatic cancer, and ovarian cancer and in ovarian cancer patient-derived cells, we analyzed stem cell phenotype and tumor growth via mRNA, miRNA, and protein expression, spheroid formation, and growth in patient-derived xenografts. We show that treatment with EMT-promoting growth factors or SNAI1 overexpression increased stemness and reduced let-7 expression, while SNAI1 knockdown reduced stemness and restored let-7 expression. Rescue experiments demonstrate that the pro-stemness effects of SNAI1 are mediated via let-7. In vivo, nanoparticle-delivered siRNA successfully knocked down SNAI1 in orthotopic patient-derived xenografts, accompanied by reduced stemness and increased let-7 expression, and reduced tumor burden. Chromatin immunoprecipitation demonstrated that SNAI1 binds the promoters of various let-7 family members, and luciferase assays revealed that SNAI1 represses let-7 transcription. In conclusion, the SNAI1/let-7 axis is an important component of stemness pathways in cancer cells, and this study provides a rationale for future work examining this axis as a potential target for cancer stem cell-specific therapies.

Sign in / Sign up

Export Citation Format

Share Document