Vorinostat targets UBE2C to reverse epithelial-mesenchymal transition and control cervical cancer growth through the ubiquitination pathway

Abstract Background Slug (Snai2) is a pivotal player in initiating epithelial-mesenchymal transition (EMT) through its trans-suppression effect on E-cadherin in various normal and malignant cells. In this study, the positive effect of Slug on promoting cell motility and metastasis in cervical cancer was further confirmed in this study. Methods RNA-Seq was performed to explore the potential molecules that participate in Slug-mediated EMT in cervical cancer cells. The negative correlation between Slug and EpCAM expression in cervical cancer cells was detected in this study, and linked them with in vitro migration and invasion assay, in vivo metastasis experiments, luciferase reporter assay and Chromatin immunoprecipitation. Results Transcriptome sequencing analysis revealed that epithelial cell adhesion molecule (EpCAM) was significantly decreased in Slug-overexpressing SiHa cells. Simultaneously, an absence of EpCAM expression was observed in Slug-overexpressing cells. Further studies revealed the trans-suppression effect of Slug on EpCAM through its binding to the E-boxes in the proximal promoter region of EpCAM in cervical cancer cells. Restoring EpCAM in Slug-overexpressing cells by transiently transfecting an EpCAM recombinant plasmid attenuated cell motility and promoted cell growth. Moreover, the negative correlation between Slug and EpCAM expression in human squamous cervical carcinoma (SCC) samples was verified by using Pearson correlation analysis. Conclusions These results demonstrated that the absence of EpCAM under Slug expression in cervical cancer cells probably participated in Slug-regulated EMT and further promoted tumor metastasis. Additionally, this study supports a potential way for Slug to initiate EMT progression in cervical cancer cells in addition to inhibiting E-cadherin.

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TMEM45A Affects Proliferation, Apoptosis, Epithelial-Mesenchymal Transition, Migration, Invasion and Cisplatin Resistance of HPV-Positive Cervical Cancer Cell Lines

Biochemical Genetics ◽

10.1007/s10528-021-10094-3 ◽

2021 ◽

Author(s):

Yan Liu ◽

Lu Liu ◽

Zhao-Xia Mou

Keyword(s):

Cervical Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Cisplatin Resistance ◽

Epithelial Mesenchymal Transition ◽

Cancer Cell Lines ◽

Cervical Cancer Cell ◽

Mesenchymal Transition

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The Impacts of Bone Marrow Mesenchymal Stem Cells (BMSCs)-Derived Periostin on Epithelial-Mesenchymal Transition (EMT) of Cervical Cancer Cells

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2022.2958 ◽

2022 ◽

Vol 12 (4) ◽

pp. 820-826

Author(s):

Chengyong Wu ◽

Weifeng Wei ◽

Jing Li ◽

Shenglin Peng

Keyword(s):

Cervical Cancer ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Signal Transduction Pathway ◽

Underlying Mechanism ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Essential Components ◽

Cervical Cancer Cells ◽

E Cadherin

Epithelial-mesenchymal transition (EMT) is closely related to the migrating and invading behaviors of cells. Periostin is one of the essential components in the extracellular matrix and can induce EMT of cells and their sequential metastasis. But its underlying mechanism is unclear. The Hela and BMSC cell lines were assigned into Periostin-mimic group, Periostin-Inhibitor group and Periostin-NC group followed by analysis of cell migration and invasion, expression of E-Cadherin, Vimentin, β-Catenin, Snail, MMP-2, MMP-9, PTEN, and p-PTEN. Cells in Periostin-mimic group exhibited lowest migration, least number of invaded cells, as well as lowest levels of Vimentin, β-Catenin, Snail, MMP-2, MMP-9, p-PTEN, Akt, p-Akt, p-GSK-3β, p-PDK1 and p-cRcf, along with highest levels of E-cadherin and PTEN. Moreover, cells in Periostin-NC group had intermediate levels of these above indicators, while, the Periostin-Inhibitor group exhibited the highest migration rate, the most number of invaded cells, and the highest levels of these proteins (P < 0.05). In conclusion, BMSCs-derived Periostin can influence the EMT of cervical cancer cells possibly through restraining the activity of the PI3K/AKT signal transduction pathway, indicating that Periostin might be a target of chemotherapy in clinics for the treatment of cervical cancer.

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Human papillomavirus oncoproteins differentially modulate epithelial-mesenchymal transition in 5-FU-resistant cervical cancer cells

Tumor Biology ◽

10.1007/s13277-016-5143-6 ◽

2016 ◽

Vol 37 (10) ◽

pp. 13137-13154 ◽

Cited By ~ 10

Author(s):

Kanchan Vishnoi ◽

Sutapa Mahata ◽

Abhishek Tyagi ◽

Arvind Pandey ◽

Gaurav Verma ◽

...

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

Cervical Cancer Cells

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APMAP Promotes Epithelial-Mesenchymal Transition and Metastasis of Cervical Cancer Cells by Activating the Wnt/β-catenin Pathway

Journal of Cancer ◽

10.7150/jca.59595 ◽

2021 ◽

Vol 12 (20) ◽

pp. 6265-6273

Author(s):

Xiuting Zhu ◽

Zijin Xiang ◽

Lingxiao Zou ◽

Xueru Chen ◽

Xiangdong Peng ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

Cervical Cancer Cells

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miR‑802 inhibits the epithelial‑mesenchymal transition, migration and invasion of cervical cancer by regulating BTF3

Molecular Medicine Reports ◽

10.3892/mmr.2020.11267 ◽

2020 ◽

Vol 22 (3) ◽

pp. 1883-1891

Author(s):

Xiuhui Wu ◽

Leng Liu ◽

Hongxia Zhang

Keyword(s):

Cervical Cancer ◽

Epithelial Mesenchymal Transition ◽

Migration And Invasion ◽

Mesenchymal Transition

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LncRNA FBXL19-AS1 promotes proliferation and metastasis of cervical cancer through upregulating COL1A1 as a sponge of miR-193a-5p

Journal of Biological Research-Thessaloniki ◽

10.1186/s40709-021-00151-8 ◽

2021 ◽

Vol 28 (1) ◽

Author(s):

Xiaoyong Huang ◽

Haiyan Shi ◽

Xinghai Shi ◽

Xuemei Jiang

Keyword(s):

Cervical Cancer ◽

Epithelial Mesenchymal Transition ◽

Malignant Tumors ◽

Mesenchymal Transition ◽

Non Coding Rna ◽

Proliferation And Metastasis ◽

Leucine Rich Repeat Protein ◽

Competitive Endogenous Rna

Abstract Background Cervical cancer (CC) is one of the most common and malignant tumors in women. In this study, we aim to explore the role and mechanism of F-box and leucine rich repeat protein 19 antisense RNA 1 (FBXL19-AS1), a novel long-chain non coding RNA (lncRNA) with marked roles in a variety of tumors, in regulating the proliferation and metastasis of CC. Methods The expression of FBXL19-AS1, miR-193a-5p and COL1A1 were detected by RT-PCR and western blot. Gain- and loss-of functional assays of FBXL19-AS1 and miR-193a-5p were performed in CC cell lines in vitro or in vivo. The proliferation, migration, invasion, apoptosis and epithelial-mesenchymal transition (EMT) of CC cells were determined. Results FBXL19-AS1 and COL1A1 were significantly up-regulated in CC tissues, while miR-193a-5p was significantly down-regulated. Overexpression of FBXL19-AS1 significantly promoted the proliferation, migration, invasion, EMT and growth of CC cells and inhibited apoptosis, while knockdown of FBXL19-AS1 had the opposite effects. On the other hand, miR-193a-5p inhibited the proliferation and metastasis of CC cells. Mechanistically, FBXL19-AS1 functioned as a competitive endogenous RNA (ceRNA) and inhibited the expression of miR-193a-5p, which targeted at the 3’-UTR site of COL1A1 and negatively regulated COL1A1 expression. Conclusions FBXL19-AS1 promotes the proliferation and metastasis of CC cells by sponging miR-193a-5p and up-regulating COL1A1.

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