scholarly journals Synergetic Effects of Intronic Mature miR-944 and ΔNp63 Isoforms on Tumorigenesis in a Cervical Cancer Cell Line

2020 ◽  
Vol 21 (16) ◽  
pp. 5612
Author(s):  
Jungho Kim ◽  
Sunyoung Park ◽  
Yunhee Chang ◽  
Kwang Hwa Park ◽  
Hyeyoung Lee
Keyword(s):  
Cervical Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Cell Line ◽  
Gene Clusters ◽  
Figo Stage ◽  
Cervical Cancer Cell Line ◽  
Mesenchymal Transition ◽  
Gynecology And Obstetrics ◽  
Simultaneous Inhibition ◽  
Cancer Tissues

miR-944 is located in an intron of the tumor protein p63 gene (TP63). miR-944 expression levels in cervical cancer tissues are significantly higher than in normal tissues and are associated with tumor size, International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, and survival. However, associations of miR-944 with its host gene, TP63, which encodes TAp63 and ΔNp63, in cervical cancer have not been fully investigated. A positive correlation between miR-944 and ΔNp63 mRNA expression was identified in cervical cancer tissues. Furthermore, when the expression of miR-944 and ΔNp63 was simultaneously inhibited, cell proliferation-, differentiation- epithelial–mesenchymal transition (EMT)-, transcription-, and virus-associated gene clusters were shown to be significantly more active according to functional annotation analysis. Cell viability and migration were more reduced upon simultaneous inhibition with anti-miR-944 or ΔNp63 siRNA than with inhibition with anti-miR-944 or ΔNp63 siRNA alone, or scramble. In addition, Western blot analysis showed that the simultaneous inhibition of miR-944 and ΔNp63 reduced EMT by increasing the expression of epithelial markers such as claudin and by decreasing mesenchymal markers such as N-cadherin and vimentin. Slug, an EMT transcription factor, was also decreased by the simultaneous inhibition of miR-944 and ΔNp63. Thus, associations between miR-944 and ΔNp63 in cervical cancer could help to elucidate the function of this intronic microRNA and its role in carcinogenesis.

scholarly journals Circ-ABCB10 knockdown inhibits the malignant progression of cervical cancer through microRNA-128-3p/ZEB1 axis

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Wei Feng ◽  
Ruixia Guo ◽  
Dongya Zhang ◽  
Ruitao Zhang
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Epithelial Mesenchymal Transition ◽  
Figo Stage ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Mesenchymal Transition ◽  
Gynecology And Obstetrics

Abstract Aims We focused on the detailed functions of circ-ABCB10 in cervical cancer (CC) development and its mechanisms. Background The increasing findings have proposed the central roles of circular RNAs (circRNAs) in the tumorigenesis of various human cancers. Circ-ABCB10 displays promising oncogenic effect in several tumors. Methods Circ-ABCB10 and miR-128-3p production levels in CC tissues and cells were tested through RT-qPCR. The association of circ-ABCB10 expression with clinicopathologic parameters of CC patients was statistically analyzed. Cell proliferation, invasion, apoptosis, and epithelial-mesenchymal transition (EMT) were evaluated by MTT, transwell invasion assays, flow cytometry analyses, and western blot examination of EMT markers. The binding activity between miR-128-3p and circ-ABCB10 or zinc finger E-box binding homeobox 1 (ZEB1) was explored through pull-down assay or luciferase reporter assay. The influence of circ-ABCB10 on CC tumorigenesis was evaluated by in vivo xenograft experiments. Results The elevated circ-ABCB10 expression was determined in CC tissues and cells. Moreover, higher production level of circ-ABCB10 was close related to lymph-node metastasis, Federation of Gynecology and Obstetrics (FIGO) stage, and tumor size in CC patients. Loss of circ-ABCB10 weakened cell proliferative and invasive abilities, inhibited EMT, and induced apoptosis in CC. Loss of circ-ABCB10 inhibited ZEB1 expression by serving as a sponge of miR-128-3p in CC cells. Circ-ABCB10 sponged miR-128-3p to enhance cell proliferation, invasion, EMT and inhibit apoptosis in CC cells. Xenograft tumor assays confirmed that circ-ABCB10 knockdown inhibited CC tumor growth. Conclusion Our study suggests that circ-ABCB10 depletion inhibits proliferation, invasion and EMT and promotes apoptosis of cervical cancer cells through miR-128-3p/ZEB1 axis and represses CC tumor growth.

scholarly journals Overexpression of the nucleoporin Nup88 stimulates migration and invasion of HeLa cells

2021 ◽  
Author(s):  
Masaki Makise ◽  
Ryota Uchimura ◽  
Kumiko Higashi ◽  
Yasumi Mashiki ◽  
Rikako Shiraishi ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cell ◽  
Hela Cells ◽  
Malignant Tumors ◽  
Cancer Cell Line ◽  
Migration And Invasion ◽  
Nuclear Pore ◽  
Cervical Cancer Cell Line ◽  
Invasive Ability ◽  
Mesenchymal Transition

AbstractElevated expression of the nucleoporin Nup88, a constituent of the nuclear pore complex, is seen in various types of malignant tumors, but whether this overexpression contributes to the malignant phenotype has yet to be determined. Here, we investigated the effect of the overexpression of Nup88 on the migration and invasion of cervical cancer HeLa cells. The overexpression of Nup88 promoted a slight but significant increase in both migration and invasion, whereas knockdown of Nup88 by RNA interference suppressed these phenotypes. The observed phenotypes in Nup88-overexpressing HeLa cells were not due to the progression of the epithelial-to-mesenchymal transition or activation of NF-κB, which are known to be important for cell migration and invasion. Instead, we identified an upregulation of matrix metalloproteinase-12 (MMP-12) at both the gene and protein levels in Nup88-overexpressing HeLa cells. Upregulation of MMP-12 protein by the overexpression of Nup88 was also observed in one other cervical cancer cell line and two prostate cancer cell lines but not 293 cells. Treatment with a selective inhibitor against MMP-12 enzymatic activity significantly suppressed the invasive ability of HeLa cells induced by Nup88 overexpression. Taken together, our results suggest that overexpression of Nup88 can stimulate malignant phenotypes including invasive ability, which is promoted by MMP-12 expression.

scholarly journals MiR-1179 is downregulated in cervical cancer and its overexpression suppresses cancer cells invasion by targeting CHAF1A/ZEB1

2021 ◽  
Author(s):  
Fahui Lv ◽  
Youwen Zhong ◽  
Ling Sang ◽  
Xiaoling Wu
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Anticancer Effect ◽  
Mesenchymal Transition ◽  
E Box ◽  
Cervical Cancer Cells ◽  
Assembly Factor ◽  
Direct Target ◽  
Cancer Tissues

The anticancer effect of miR-1179 has been extensively studied in many tumors. The mechanism of miR-1179 action in cervical cancer, however, remains largely unknown. In the present study, miR-1179 was downregulated in both cervical cancer cell lines and cancer tissues. In addition, miR-1179 mimic suppressed cancer cells invasion and epithelial-mesenchymal transition (EMT) in cervical cancer SiHa and Caski cells. We found that chromatin assembly factor 1 subunit A (CHAF1A) might be a direct target of miR-1179 and could be regulated by miR-1179. Furthermore, CHAF1A shRNA suppressed the cervical cancer cells invasion and the expression of EMT-promoted proteins. Reversely, CHAF1A overexpression not only promoted cervical cancer cells invasion but also upregulated the level of Zinc finger E‐box binding protein 1 (ZEB1), an EMT-related protein. The induction of ZEB1 could be counteracted by miR-1179 overexpression. It was observed that in cervical cancer patients’ tissues, miR-1179 was downregulated while the pathway of CHAF1A/ZEB1 was upregulated. In summary, our research indicated that the miR-1179 might regulate CHAF1A/ZEB1 axis and inhibit the invasion of cervical cancer cells.

scholarly journals ZEB2 facilitates peritoneal metastasis by regulating the invasiveness and tumorigenesis of cancer stem-like cells in high-grade serous ovarian cancers

Oncogene ◽  
2021 ◽  
Author(s):  
Yiying Li ◽  
He Fei ◽  
Qiwang Lin ◽  
Fan Liang ◽  
Yanan You ◽  
...  
Keyword(s):  
Peritoneal Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Underlying Mechanism ◽  
Figo Stage ◽  
High Grade ◽  
Mesenchymal Transition ◽  
Ovarian Cancers ◽  
Gynecology And Obstetrics ◽  
Epithelial Marker ◽  
Zeb2 Expression

Abstract Peritoneal metastasis is a common issue in the progression of high-grade serous ovarian cancers (HGSOCs), yet the underlying mechanism remains unconfirmed. We demonstrated that ZEB2, the transcription factor of epithelial–mesenchymal transition (EMT), was upregulated in ascites cells from HGSOC patients and in CD133+ cancer stem-like cells (CSLCs) from epithelial ovarian cancer (EOC) cell lines. SiRNA-mediated knockdown of ZEB2 in EOC cells decreased the percentage of CSLCs and reduced the colony forming potential, cell invasion capacity and expression of pluripotent genes Oct4 and Nanog. Inhibition of ZEB2 also induced cellular apoptosis and impacted the tumorigenicity of ovarian CSLCs. The mesenchymal markers N-cadherin and vimentin were downregulated, while the epithelial marker E-cadherin was upregulated after ZEB2 knockdown. MiR-200a, a molecule that downregulates ZEB2, had the opposite effect of ZEB2 expression in EOC-CSLCs. A retrospective study of 98 HGSOC patients on the relationship of ascites volume, pelvic and abdominal metastasis, International Federation of Gynecology and Obstetrics (FIGO) stage and the malignant involvement of abdominal organs and lymph nodes was performed. Patients with high expression of ZEB2 in tumour tissues had a higher metastasis rate and a poorer prognosis than those with low expression. The parameters of ZEB2 expression and ascites volume were strongly linked with the prognostic outcome of HGSOC patients and had higher hazard ratios. These findings illustrated that ZEB2 facilitates the invasive metastasis of EOC-CSLCs and can predict peritoneal metastasis and a poor prognosis in HGSOC patients.

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