Circular RNA circMTO1 suppresses bladder cancer metastasis by sponging miR-221 and inhibiting epithelial-to-mesenchymal transition

Circular RNA (circRNA) is a newly discovered endogenous non-coding RNA (ncRNA), which is characterized with a closed circular structure. A growing body of evidence has verified the vital roles of circRNAs in human cancer. In this research, we selected circPPP1CB as a study object by circRNA sequencing and quantitative real-time PCR (qRT-PCR) validation in human bladder cancer (BC). CircPPP1CB is downregulated in BC and is negatively correlated with clinical stages and histological grades. Functionally, circPPP1CB modulated cell growth, metastasis, and epithelial-to-mesenchymal transition (EMT) process in vitro and in vivo. Mechanically, we performed various experiments to verify the circPPP1CB/miR-1307-3p/SMG1 regulatory axis. Taken together, our results demonstrated that circPPP1CB participates in tumor growth, metastasis, and EMT process by interacting with the miR-1307-3p/SMG1 axis, and that circPPP1CB might be a novel therapeutic target and diagnostic biomarker in human BC.

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CUL4B promotes bladder cancer metastasis and induces epithelial-to-mesenchymal transition by activating the Wnt/β-catenin signaling pathway

Oncotarget ◽

10.18632/oncotarget.20455 ◽

2017 ◽

Vol 8 (44) ◽

pp. 77241-77253 ◽

Cited By ~ 12

Author(s):

Xia-Wa Mao ◽

Jia-Quan Xiao ◽

Gang Xu ◽

Zhong-Yi Li ◽

Hui-Feng Wu ◽

...

Keyword(s):

Bladder Cancer ◽

Signaling Pathway ◽

Cancer Metastasis ◽

Epithelial To Mesenchymal Transition ◽

Mesenchymal Transition

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Circular RNA hsa_circ_0001178 facilitates the invasion and metastasis of colorectal cancer through upregulating ZEB1 via sponging multiple miRNAs

Biological Chemistry ◽

10.1515/hsz-2019-0350 ◽

2020 ◽

Vol 401 (4) ◽

pp. 487-496 ◽

Cited By ~ 6

Author(s):

Chunfeng Ren ◽

Zhenmin Zhang ◽

Shunhua Wang ◽

Weitao Zhu ◽

Peiguo Zheng ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Metastasis ◽

Epithelial To Mesenchymal Transition ◽

Underlying Mechanism ◽

Circular Rna ◽

Mechanistic Study ◽

Mesenchymal Transition ◽

Promising Treatment

AbstractMetastasis is the main cause of increasing cancer morbidity and mortality. However, the underlying mechanism of cancer metastasis remains largely unknown. In the present study, we identified one circular RNA (circRNA) closely related to the metastasis of colorectal cancer (CRC), namely hsa_circ_0001178. CRC patients with high hsa_circ_0001178 were more prone to have metastatic clinical features, advanced TNM stage and adverse prognosis. Stable knockdown of hsa_circ_0001178 significantly weakened CRC cell migratory and invasive capabilities in vitro as well as lung and liver metastases in vivo. Mechanistic study revealed that hsa_circ_0001178 acted as a competing endogenous RNA (ceRNA) for miR-382/587/616 to upregulate ZEB1 (a key trigger of epithelial-to-mesenchymal transition), thereby promoting CRC metastatic dissemination. Of note, ZEB1 could also increase hsa_circ_0001178 expression via physically binding to hsa_circ_0001178 promoter region. Collectively, our data uncover the crucial role of hsa_circ_0001178 in CRC metastasis, and targeted therapy based on this positive feedback ceRNA axis may be a promising treatment for metastatic CRC patients.

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The Epithelial to Mesenchymal Transition Related Gene Calumenin Is an Adverse Prognostic Factor of Bladder Cancer Correlated With Tumor Microenvironment Remodeling, Gene Mutation, and Ferroptosis

Frontiers in Oncology ◽

10.3389/fonc.2021.683951 ◽

2021 ◽

Vol 11 ◽

Author(s):

YiHeng Du ◽

WenHao Miao ◽

Xiang Jiang ◽

Jin Cao ◽

Bo Wang ◽

...

Keyword(s):

Bladder Cancer ◽

Tumor Microenvironment ◽

Gene Mutation ◽

Immune Cells ◽

Molecular Mechanisms ◽

Cancer Metastasis ◽

Epithelial To Mesenchymal Transition ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

The Impact

The tumor microenvironment (TME) plays a critical regulatory role in bladder cancer (BLCA) progression and metastasis. Epithelial-mesenchymal transition (EMT) presents as an essential mechanism of tumor invasion and metastasis. Accumulating pieces of evidence indicated that several microenvironmental factors, including fibroblasts, endothelial, and immune cells, induced EMT in tumor cells. As a hallmark gene of the EMT process, calumenin (CALU) was previously reported to directly impact cancer metastasis. However, the functions and molecular mechanisms of CALU have been rarely reported in BLCA. By multi-omics bioinformatics analysis of 408 TCGA BLCA patients, we demonstrated that CALU was an independent risk factor for BLCA outcome. Subsequently, we verified the correlation of CALU with cancer-associated fibroblasts (CAFs) and tumor-infiltrating immune cells. The results suggested a positive correlation of CALU with CAFs, CD8+ T cells and macrophages. Also, CALU was significantly associated with multiple immune checkpoint-related genes, which ultimately influenced patients’ responsiveness to immunotherapy. Further, we found that the impact of CALU on BLCA prognosis might also be correlated with gene mutations and ferroptosis. Finally, we validated the roles of CALU by single-cell RNA sequencing, PCR and immunohistochemistry. In conclusion, we found that CALU affected BLCA prognosis associated with multiple mechanisms, including TME remodeling, gene mutation and ferroptosis. Further studies on CALU may provide new targets for BLCA immunotherapy and precision medicine.

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Ovalitenone Inhibits the Migration of Lung Cancer Cells via the Suppression of AKT/mTOR and Epithelial-to-Mesenchymal Transition

Molecules ◽

10.3390/molecules26030638 ◽

2021 ◽

Vol 26 (3) ◽

pp. 638

Author(s):

Kittipong Sanookpan ◽

Nongyao Nonpanya ◽

Boonchoo Sritularak ◽

Pithi Chanvorachote

Keyword(s):

Lung Cancer ◽

Cell Migration ◽

Cancer Cells ◽

Colony Formation ◽

Cancer Metastasis ◽

Epithelial To Mesenchymal Transition ◽

A549 Cells ◽

Lung Cancer Cells ◽

Migration And Invasion ◽

Mesenchymal Transition

Cancer metastasis is the major cause of about 90% of cancer deaths. As epithelial-to-mesenchymal transition (EMT) is known for potentiating metastasis, this study aimed to elucidate the effect of ovalitenone on the suppression of EMT and metastasis-related behaviors, including cell movement and growth under detached conditions, and cancer stem cells (CSCs), of lung cancer cells. Methods: Cell viability and cell proliferation were determined by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazo-liumbromide (MTT) and colony formation assays. Cell migration and invasion were analyzed using a wound-healing assay and Boyden chamber assay, respectively. Anchorage-independent cell growth was determined. Cell protrusions (filopodia) were detected by phalloidin-rhodamine staining. Cancer stem cell phenotypes were assessed by spheroid formation. The proteins involved in cell migration and EMT were evaluated by Western blot analysis and immunofluorescence staining. Results: Ovalitenone was used at concentrations of 0–200 μM. While it caused no cytotoxic effects on lung cancer H460 and A549 cells, ovalitenone significantly suppressed anchorage-independent growth, CSC-like phenotypes, colony formation, and the ability of the cancer to migrate and invade cells. The anti-migration activity was confirmed by the reduction of filopodia in the cells treated with ovalitenone. Interestingly, we found that ovalitenone could significantly decrease the levels of N-cadherin, snail, and slug, while it increased E-cadherin, indicating EMT suppression. Additionally, the regulatory signaling of focal adhesion kinase (FAK), ATP-dependent tyrosine kinase (AKT), the mammalian target of rapamycin (mTOR), and cell division cycle 42 (Cdc42) was suppressed by ovalitenone. Conclusions: The results suggest that ovalitenone suppresses EMT via suppression of the AKT/mTOR signaling pathway. In addition, ovalitenone exhibited potential for the suppression of CSC phenotypes. These data reveal the anti-metastasis potential of the compound and support the development of ovalitenone treatment for lung cancer therapy.

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