scholarly journals Circular RNA circHERC4 as a novel oncogenic driver to promote tumor metastasis via the miR-556-5p/CTBP2/E-cadherin axis in colorectal cancer

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jiehua He ◽  
Ziqiang Chu ◽  
Wei Lai ◽  
Qiusheng Lan ◽  
Yujie Zeng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Tumor Metastasis ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Tumor Grade ◽  
Circular Rna ◽  
Advanced Tumor ◽  
E Cadherin

Abstract Background The main cause of death in colorectal cancer patients is metastasis. Accumulating evidences suggest that circRNA plays pivotal roles in cancer initiation and development. However, the underlying molecular mechanisms of circRNAs that orchestrate cancer metastasis remain vague and need further clarification. Methods Two paired CRC and adjacent normal tissues were used to screen the upregulated circRNAs by circRNA-seq; then, cell invasion assay was applied to confirm the functional invasion-related circRNAs. According to the above methods, circHERC4 (hsa_circ_0007113) was selected for further research. Next, we investigated the clinical significance of circHERC4 in a large cohort of patients with CRC. The oncogenic activity of circHERC4 was investigated in both CRC cell lines and animal xenograft studies. Finally, we explored the molecular mechanisms underlying circHERC4 as a malignant driver. Results We demonstrated that circHERC4 was aberrantly elevated in CRC tissues (P < 0.001), and was positively associated with lymph node metastasis and advanced tumor grade (P < 0.01). Notably, the expression of circHERC4 was associated with worse survival in patients with CRC. Silencing of circHERC4 significantly inhibited the proliferation and migration of two highly aggressive CRC cell lines and reduced liver and lung metastasis in vivo. Mechanistically, we revealed that circHERC4 inactivated the tumor suppressor, miR-556-5p, leading to the activation of CTBP2/E-cadherin pathway which promotes tumor metastasis in CRC. Conclusions CircHERC4 exerts critical roles in promoting tumor aggressiveness through miR-556-5p/CTBP2/E-cadherin pathway and is a prognostic biomarker of the disease, suggesting that circHERC4 may serve as an exploitable therapeutic target for patients with CRC.

scholarly journals ARID1A Regulates E-Cadherin Expression in Colorectal Cancer Cells: A Promising Candidate Therapeutic Target

2021 ◽  
Author(s):  
Mehran Erfani ◽  
Mozhdeh Zamani ◽  
Seyed Younes Hosseini ◽  
Zohreh Mostafavi-Pour ◽  
Sayed Mohammad Shafiee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Therapeutic Target ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Promising Candidate ◽  
Mesenchymal Transition ◽  
The Impact ◽  
Hct116 Cells ◽  
E Cadherin

Abstract Background Metastasis is a major cause of death in colorectal cancer (CRC) patients, and the epithelial–mesenchymal transition (EMT) has been known to be a crucial event in cancer metastasis. Downregulated expression of AT-rich interaction domain-containing protein 1A (ARID1A), a bona fide tumor suppressor gene, plays an important role in promoting EMT and CRC metastasis, but the underlying molecular mechanisms remain poorly understood. Here, we evaluated the impact of ARID1A knockdown and overexpression on the expression of EMT‑related genes, E-cadherin and β-catenin, in human CRC cells.Methods and Results The expression levels of ARID1A, E-cadherin and β-catenin in CRC cell lines were detected via real-time quantitative PCR (qPCR) and western blot. ARID1A overexpression and shRNA-mediated knockdown were performed to indicate the effect of ARID1A expression on E-cadherin and β-catenin expression in CRC cell lines. The effect of ARID1A knockdown on the migration ability of HCT116 cells was assessed using wound-healing assay. We found that the mRNA and protein expression of adhesive protein E-cadherin was remarkably downregulated in response to shRNA-mediated ARID1A knockdown in HCT116 and HT29 cells. Conversely, overexpression of ARID1A in SW48 cells significantly increased E-cadherin expression. In addition, ARID1A silencing promoted the migration of HCT116 cells. ARID1A knockdown and overexpression did not alter the level of β-catenin expression.Conclusion Our study demonstrates that E-cadherin levels were closely correlated with ARID1A expression. Thus, ARID1A downregulation may promote CRC metastasis through decreasing EMT‑related protein E-cadherin and promoting epithelial cell movement. ARID1A could represent a promising candidate therapeutic target for CRC.

scholarly journals Dietary delphinidin inhibits human colorectal cancer metastasis associating with upregulation of miR-204-3p and suppression of the integrin/FAK axis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Chi-Chou Huang ◽  
Chia-Hung Hung ◽  
Tung-Wei Hung ◽  
Yi-Chieh Lin ◽  
Chau-Jong Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Migration And Invasion ◽  
Colorectal Cancer Metastasis ◽  
Β3 Integrin ◽  
Underlying Mechanisms ◽  
Sw620 Cells

AbstractDelphinidin is a flavonoid belonging to dietary anthocyanidin family that has been reported to possess diverse anti-tumoral activities. However, the effects of delphinidin on colorectal cancer (CRC) cells and the underlying mechanisms are not fully understood. Thus, we aimed to investigate the anti-cancer activity of delphinidin in CRC cells and the underlying molecular mechanisms. The effects of delphinidin on the viability, metastatic characteristics, signaling, and microRNA (miR) profile of human CRC cell lines used were analyzed. In vivo metastasis was also evaluated using xenograft animal models. Our findings showed that delphinidin (<100 μM) inhibited the colony formation of DLD-1, SW480, and SW620 cells, but non-significantly affected cell viability. Delphinidin also suppressed the migratory ability and invasiveness of the tested CRC cell lines, downregulated integrin αV/β3 expression, inhibited focal adhesion kinase (FAK)/Src/paxillin signaling, and interfered with cytoskeletal construction. Analysis of the miR expression profile revealed a number of miRs, particularly miR-204-3p, that were significantly upregulated and downregulated by delphinidin. Abolishing the expression of one upregulated miR, miR-204-3p, with an antagomir restored delphinidin-mediated inhibition of cell migration and invasiveness in DLD-1 cells as well as the αV/β3-integrin/FAK/Src axis. Delphinidin also inhibited the lung metastasis of DLD-1 cells in the xenograft animal model. Collectively, these results indicate that the migration and invasion of CRC cells are inhibited by delphinidin, and the mechanism may involve the upregulation of miR-204-3p and consequent suppression of the αV/β3-integrin/FAK axis. These findings suggest that delphinidin exerts anti-metastatic effects in CRC cells by inhibiting integrin/FAK signaling and indicate that miR-204-3p may play an important role in CRC metastasis.

scholarly journals LncRNA DANCR functions as a competing endogenous RNA to regulate RAB1A expression by sponging miR-634 in glioma

2018 ◽  
Vol 38 (1) ◽  
Author(s):  
Dawei Xu ◽  
Jian Yu ◽  
Guojun Gao ◽  
Guangjian Lu ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Cell Lines ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Glioma Cells ◽  
Tumor Grade ◽  
Underlying Mechanism ◽  
Luciferase Reporter ◽  
Biological Functions ◽  
Advanced Tumor ◽  
Rna Immunoprecipitation

Long noncoding RNA (lncRNA) differentiation antagonizing nonprotein coding RNA (DANCR) plays important regulatory roles in many solid tumors. However, the effect of DANCR in glioma progression and underlying molecular mechanisms were not entirely explored. In the present study, we determined the expression of DANCR in glioma tissues and cell lines using qRT-PCR and further defined the biological functions. Furthermore, we used luciferase reporter assay, Western blot, and RNA immunoprecipitation (RIP) to explore the underlying mechanism. Our results showed that DANCR was significantly up-regulated in glioma tissues and cell lines (U251, U118, LN229, and U87MG). High DANCR expression was correlated with advanced tumor grade. Inhibition of DANCR suppressed the glioma cells proliferation and induced cells arrested in the G0/G1 phase. In addition, we verified that DANCR could directly interact with miR-634 in glioma cells and this interaction resulted in the inhibition of downstream of RAB1A expression. The present study demonstrated that DANCR/miR-634/RAB1A axis plays crucial roles in the progression of glioma, and DANCR might potentially serve as a therapeutic target for the treatment of glioma patients.

scholarly journals MeCP2 Promotes Colorectal Cancer Metastasis by Modulating ZEB1 Transcription

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 758
Author(s):  
Dan Luo ◽  
Wei Ge
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
The Cancer Genome Atlas ◽  
Mobility Shift ◽  
Migration Ability ◽  
Invasion And Migration ◽  
Distant Organ Metastasis

Background: Recurrence and distant organ metastasis is a major cause of death in colorectal cancer (CRC); however, the underlying molecular mechanisms regulating this phenomenon are poorly understood. MeCP2 is a key epigenetic regulator and is amplified in many types of cancer. Its role in CRC and the molecular mechanisms underlying its action remain unknown. Methods: We used western blot and immunohistochemistry to detect MeCP2 expression in CRC tissues, and then investigated its biological functions in vitro and in vivo. Chromatin immunoprecipitation, co-immunoprecipitation, and electrophoretic mobility shift assays were used to detect the associations among MeCP2 (Methyl-CpG binding protein 2), SPI1 (Spi-1 Proto-Oncogene), and ZEB1 (Zinc Finger E-Box Binding Homeobox 1). Results: Using the Cancer Genome Atlas and Oncomine databases, we found MeCP2 expression was upregulated in CRC tissues and this upregulation was related to poor prognosis. Meanwhile, MeCP2 depletion (KO/KD) in CRC cells significantly inhibited stem cell frequency, and invasion and migration ability in vitro, and suppressed CRC metastasis in vivo. Mechanistically, we show MeCP2 binds to the transcription factor SPI1, and aids its recruitment to the ZEB1 promoter. SPI1 then facilitates ZEB1 expression at the transcription level. In turn, ZEB1 induces the expression of MMP14, CD133, and SOX2, thereby maintaining CRC stemness and metastasis. Conclusions: MeCP2 is a novel regulator of CRC metastasis. MeCP2 suppression may be a promising therapeutic strategy in CRC.

scholarly journals LOXL1 modulates the malignant progression of colorectal cancer by inhibiting the transcriptional activity of YAP

2020 ◽  
Author(s):  
Lin Hu ◽  
Jing Wang ◽  
Yunliang Wang ◽  
Linpeng Wu ◽  
Chao Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Colony Formation ◽  
Transcriptional Activity ◽  
Tumour Growth ◽  
Molecular Mechanisms ◽  
Migration And Invasion

Abstract Background: LOX-like 1 (LOXL1) is a lysyl oxidase, and emerging evidence has revealed its effect on malignant cancer progression. However, its role in colorectal cancer (CRC) and the underlying molecular mechanisms have not yet been elucidated. Methods: LOXL1 expression in colorectal cancer was detected by immunohistochemistry, western blotting and real-time PCR. In vitro , colony formation, wound healing, migration and invasion assays were performed to investigate the effects of LOXL1 on cell proliferation, migration and invasion. In vivo , metastasis models and mouse xenografts were used to assess tumorigenicity and metastasis ability. Molecular biology experiments were utilized to reveal the underlying mechanisms by which LOXL1 modulates the Hippo pathway. Results: LOXL1 was highly expressed in normal colon tissues compared with cancer tissues. In vitro, silencing LOXL1 in CRC cell lines dramatically enhanced migration, invasion, and colony formation, while overexpression of LOXL1 exerted the opposite effects. The results of the in vivo experiments demonstrated that the overexpression of LOXL1 in CRC cell lines drastically inhibited metastatic progression and tumour growth. Mechanistically, LOXL1 inhibited the transcriptional activity of Yes-associated protein (YAP) by interacting with MST1/2 and increasing the phosphorylation of MST1/2. Conclusions: LOXL1 may function as an important tumour suppressor in regulating tumour growth, invasion and metastasis via negative regulation of YAP activity.

scholarly journals LOXL1 modulates the malignant progression of colorectal cancer by inhibiting the transcriptional activity of YAP

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Lin Hu ◽  
Jing Wang ◽  
Yunliang Wang ◽  
Linpeng Wu ◽  
Chao Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Colony Formation ◽  
Transcriptional Activity ◽  
Tumour Growth ◽  
Molecular Mechanisms ◽  
Migration And Invasion

Abstract Background LOX-like 1 (LOXL1) is a lysyl oxidase, and emerging evidence has revealed its effect on malignant cancer progression. However, its role in colorectal cancer (CRC) and the underlying molecular mechanisms have not yet been elucidated. Methods LOXL1 expression in colorectal cancer was detected by immunohistochemistry, western blotting and real-time PCR. In vitro, colony formation, wound healing, migration and invasion assays were performed to investigate the effects of LOXL1 on cell proliferation, migration and invasion. In vivo, metastasis models and mouse xenografts were used to assess tumorigenicity and metastasis ability. Molecular biology experiments were utilized to reveal the underlying mechanisms by which LOXL1 modulates the Hippo pathway. Results LOXL1 was highly expressed in normal colon tissues compared with cancer tissues. In vitro, silencing LOXL1 in CRC cell lines dramatically enhanced migration, invasion, and colony formation, while overexpression of LOXL1 exerted the opposite effects. The results of the in vivo experiments demonstrated that the overexpression of LOXL1 in CRC cell lines drastically inhibited metastatic progression and tumour growth. Mechanistically, LOXL1 inhibited the transcriptional activity of Yes-associated protein (YAP) by interacting with MST1/2 and increasing the phosphorylation of MST1/2. Conclusions LOXL1 may function as an important tumour suppressor in regulating tumour growth, invasion and metastasis via negative regulation of YAP activity. Graphical abstract

scholarly journals lncRNA LINC00460 Functions as a Competing Endogenous RNA and Regulates Expression of BGN by Sponging miR-149-5p in Colorectal Cancer

2021 ◽  
Vol 20 ◽  
pp. 153303382096423
Author(s):  
Tingyan Ruan ◽  
Shourong Lu ◽  
Junying Xu ◽  
Ju-Ying Zhou
Keyword(s):  
Colorectal Cancer ◽  
Tumor Metastasis ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Binding Interaction ◽  
Expression Levels ◽  
Cancer Tissues

Background and Aim: There are an increasing number of studies indicating the important roles served by long non-coding RNAs (lncRNAs) in the development of different types of cancer. LINC00460 is a novel identified lncRNA that was found to be upregulated in colorectal cancer. However, the biological roles of LINC00460 in colorectal cancer have yet to be fully elucidated. This study was aimed to investigate the functions and molecular mechanisms of LINC00460 on colorectal cancer metastasis. Methods: Expression of LINC00460 and biglycan (BGN) in colorectal cancer tissues and cell lines were quantified by real time PCR or western blotting assay. Cell migration and invasion assays were performed to determine the effect of LINC00460 on tumor metastasis in vitro. The binding interaction between microRNA-149-5p and LINC00460 was revealed by luciferase reporter assay. Results: In the present study, lncRNA LINC00460 was shown to be upregulated in colorectal cancer tissues, and overexpression of LINC00460 significantly promoted metastasis of colorectal cancer in vitro. Furthermore, miR-149-5p interacted with LINC00460, and they negatively regulated expression of each other. Transfection of miR-149-5p mimics partially counteracted the tumor metastasis-promoting effects induced by LINC00460 overexpression. Finally, overexpression of LINC00460 upregulated the expression levels of biglycan, a target gene of miR-149-5p, which has also been identified as an oncogenic driver in colorectal cancer. Conclusion: Taken together, the present study demonstrated that LINC00460 promoted metastasis of CRC by sponging miR-149-5p and thereby affecting biglycan expression levels.

scholarly journals Curcumin Suppresses Metastasis via Sp-1, FAK Inhibition, and E-Cadherin Upregulation in Colorectal Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-17 ◽  
Author(s):  
Chun-Chieh Chen ◽  
Munisamy Sureshbabul ◽  
Huei-Wen Chen ◽  
Yu-Shuang Lin ◽  
Jen-Yi Lee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Public Health Problem ◽  
Stress Factors ◽  
Dependent Manner ◽  
Extracellular Matrix Components ◽  
E Cadherin

Colorectal cancer (CRC) is a serious public health problem that results due to changes of diet and various environmental stress factors in the world. Curcumin is a traditional medicine used for treatment of a wide variety of tumors. However, antimetastasis mechanism of curcumin on CRC has not yet been completely investigated. Here, we explored the underlying molecular mechanisms of curcumin on metastasis of CRC cellsin vitroandin vivo. Curcumin significantly inhibits cell migration, invasion, and colony formationin vitroand reduces tumor growth and liver metastasisin vivo. We found that curcumin suppresses Sp-1 transcriptional activity and Sp-1 regulated genes including ADEM10, calmodulin, EPHB2, HDAC4, and SEPP1 in CRC cells. Curcumin inhibits focal adhesion kinase (FAK) phosphorylation and enhances the expressions of several extracellular matrix components which play a critical role in invasion and metastasis. Curcumin reduces CD24 expression in a dose-dependent manner in CRC cells. Moreover, E-cadherin expression is upregulated by curcumin and serves as an inhibitor of EMT. These results suggest that curcumin executes its antimetastasis function through downregulation of Sp-1, FAK, and CD24 and by promoting E-cadherin expression in CRC cells.

scholarly journals Pseudogene OCT4-pg5 Upregulates OCT4B Expression To Promote Bladder Cancer Progression By Competing With miR-145

2021 ◽  
Author(s):  
Wuer Zhou ◽  
Yue Yang ◽  
Wei Wang ◽  
Chenglin Yang ◽  
Zhi Cao ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Tumor Grade ◽  
Luciferase Reporter ◽  
In Vivo Experiments ◽  
Bladder Cell ◽  
Advanced Tumor

Abstract Background Octamer-binding transcription factor 4 pseudogene 5 (OCT4-pg5) contributes to tumor progression in many cancer types, but contributions to bladder cancer (BC) have not been investigated. Methods Real-time quantity PCR (RT-qPCR) was performed to measure OCT4-pg5 and OCT4B expressions in different bladder cell lines and different grades of cancer. The effects of OCT4-pg5, OCT4B and miR-145 on proliferation and metastasis were determined by in vitro and in vivo experiments. Luciferase reporter assay was carried out to reveal the interaction among OCT4-pg5, OCT4B and miR-145. Flow cytometry was performed to explore the effects of OCT4-pg5 and OCT4B expression on the cell cycle stage distribution of T24 cells. Results OCT4-pg5 expression was significantly increased in BC cell lines, which was correlated with OCT4B expression and advanced tumor grade. Overexpression of OCT4-pg5 and OCT4B promoted the proliferation and invasion of BC cells, while miR-145 suppressed these activities. Mechanically, OCT4-pg5 3’ untranslated region (3’UTR) competed for miR-145, thereby increasing OCT4B expression. In addition, OCT4-pg5 promoted EMT by activating the Wnt/β-catenin pathway and upregulating the expression levels of matrix metalloproteinases (MMPs) 2 and 9 as well as transcription factors zinc finger E-box binding homeobox (ZEB) 1 and 2. Furthermore, elevated expression of OCT4-pg5 and OCT4B reduced the sensitivity of BC cells to cisplatin by reducing apoptosis and increasing the proportion of cells in G1. Conclusions These findings indicate that OCT4-pg5/miR-145/OCT4B axis promotes the progression of BC by inducing EMT via Wnt/β-catenin pathway and enhances the cisplatin resistance. It could be prospect for the therapeutic approaches for BC.

scholarly journals LOXL1 modulates the malignant progression of colorectal cancer by inhibiting the transcriptional activity of YAP

2020 ◽  
Author(s):  
Lin Hu ◽  
Jing Wang ◽  
Yunliang Wang ◽  
Linpeng Wu ◽  
Chao Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Colony Formation ◽  
Transcriptional Activity ◽  
Tumour Growth ◽  
Molecular Mechanisms ◽  
Malignant Progression ◽  
Migration And Invasion

Abstract Background LOX-like 1 (LOXL1), as a lysyl oxidase, emerging evidences revealed the effect in cancer malignant progression. However, its role in colorectal cancer (CRC) and the underlying molecular mechanisms have not yet been elucidated. Methods LOXL1 expression in colorectal cancer was detected by immunohistochemistry, western blot and real-time PCR. In vitro , colony formation assay, wound healing assay, migration and invasion experiment were performed to investigate the effects of LOXL1 in cell proliferation, migration and invasion, respectively. In vivo , metastasis models and mouse xenograft were used to determine tumorigenicity and metastasis ability. Molecular biology experiments were utilized to reveal the underlying mechanisms of LOXL1 modulating Hippo pathway. Results LOXL1 is highly expressed in normal colon tissues compared with cancer tissues. In vitro, Silencing LOXL1 in CRC cell lines dramatically enhanced migration, invasion, and colony formation, while overexpression of LOXL1 manifested the opposite effects. Results of the in vivo experiments demonstrated that the enforced expression of LOXL1 in CRC cell lines had drastically inhibited the progression of metastasis and tumour growth. Mechanistically, LOXL1 inhibited the transcriptional activity of Yes-associated protein (YAP) was through interaction with MST1/2 and increasing the phosphorylation of MST1/2. Conclusions LOXL1 may function as an important tumour suppressor in regulating tumour growth, invasion and metastasis via negative regulating of YAP activity.

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