Quercetin inhibits the tumorigenesis of colorectal cancer cells through downregulation of hsa_circ_0006990

Abstract Background This study was intended to investigate the function of Quercetin in chemoresistant colorectal cancer (CRC) cells. In addition, this research aimed to explore the mechanism by which Quercetin regulates the malignant behavior of CRC cells. Methods To induce THP-1 cells into M2 tumor-associated macrophages (M2-TAMs), THP-1 cells were stimulated by PMA and IL-4. MDC staining was used to investigate the autophagy in M2-TAMs. Meanwhile, cell proliferation was tested by colony formation assay. In addition, wound healing and transwell assay were performed to detect the cell migration and invasion, respectively. Dual luciferase assay was used to investigate the correlation between hsa_circ_0006990 and miR-132-3p/miR-532-3p. Furthermore, mRNA and protein levels were detected by RT-qPCR and western blot, respectively. Results Quercetin suppressed autophagy of M2-TAMs. In addition, M2-TAMs significantly inhibited the apoptosis and promoted the proliferation of CRC cells, while this phenomenon was reversed by Quercetin. Meanwhile, the expression of hsa_circ_0006990 in CRC cells was decreased by M2-TAMs, while Quercetin reversed this phenomenon. Furthermore, overexpression of hsa_circ_0006990 significantly reversed the anti-tumor effect of Quercetin on CRC. Conclusion Quercetin inhibited the tumorigenesis of colorectal cancer cells through downregulation of hsa_circ_0006990. Thus, our study might shed new lights on exploring the new strategies against CRC.

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MicroRNA-490-3p inhibits migration and chemoresistance of colorectal cancer cells via targeting TNKS2

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02226-1 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Jing Li ◽

Rubing Mo ◽

Linmei Zheng

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Target Genes ◽

Chemotherapy Resistance ◽

Luciferase Assay ◽

Migration And Invasion ◽

Invasion And Migration ◽

Colorectal Cancer Cells ◽

And Migration ◽

Common Malignancy

Abstract Objective Colorectal cancer is one of the most common malignancy in the world. The oncogenesis of colorectal cancer is still not fully elucidated. It was reported that microRNA-490-3p (miR-490-3p) was closely related to the regulation of cancers. However, if miR-490-3p could also affect colorectal cancer and the specific mechanism remains unclear. Methods qRT-PCR was conducted to examine the expression of miR-490-3p. DIANA, miRDB, and TargetScan databases were used to identify target genes. LOVO and SW480 cells were transfected by miR-490-3p mimics and inhibitors. Transwell assay was used to measure cell invasion and migration. Cisplatin and fluorouracil were administered to investigate chemotherapy resistance. Western blot was used to measure TNKS2 protein expression. Binding sites were verified using the double luciferase assay. Results miR-490-3p expression was low in the colorectal cancer cells. The level of miR-490-3p was negatively correlated with cell migration and invasion of cancer cells. miR-490-3p could bind to TNKS2 mRNA 3′UTR directly. miR-490-3p can suppress cell viability and resistance to chemotherapy in colorectal cancer cells through targeting TNKS2. Conclusions miR-490-3p could affect colorectal cancer by targeting TNKS2. This study may provide a potential therapeutic target for colorectal cancer.

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Galloflavin Relieves the Malignant Behavior of Colorectal Cancer Cells in the Inflammatory Tumor Microenvironment

Frontiers in Pharmacology ◽

10.3389/fphar.2021.752118 ◽

2021 ◽

Vol 12 ◽

Author(s):

Li Guo ◽

Yi Yang ◽

Yongjia Sheng ◽

Jin Wang ◽

Wenyan Li ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Migration And Invasion ◽

High Dose ◽

Inflammatory Microenvironment ◽

Tumor Bearing ◽

Cell Metastasis ◽

Colorectal Cancer Cells ◽

Sw480 Cells ◽

Malignant Behavior

Background: In this study, we mainly aimed to explore the correlation between galloflavin and NLRP3 and its effect on colorectal cancer.Methods: NLRP3 was overexpressed in SW480 cells; LPS + ATP was used to mimic the inflammatory microenvironment. Wound healing assay and Transwell assay were utilized to detect cell migration and invasion abilities; CCK-8 assay was performed to detect cell viability alterations; colony formation assay was conducted to detect colony formation ability; Western blot was used to detect the levels of NLRP3, ASC, C-Myc, and P21. SW480 cells were pretreated with high-dose and low-dose galloflavin, followed by observation of their effects on cell metastasis and invasion. NLRP3 was knocked out in SW480 to construct the SW480-NLRP3−/− cell line, followed by high-dose galloflavin treatment and subsequent observation of cell metastasis and invasion abilities. Small molecule–protein docking and pull-down assay were performed to confirm the targeting relationship between galloflavin and NLRP3. After constructing a tumor-bearing mice model, galloflavin was intragastrically administered, followed by detection of tumor growth, expression of NLRP3 and ASC by immunohistochemistry, and tumor histopathology by H&E staining.Results: After NLRP3 overexpression and LPS/ATP induction in SW480, the cell migration and invasion abilities were significantly enhanced, and cell viability was also enhanced. The activation of NLRP3 could promote the malignant behavior of colorectal cancer cells in the inflammatory microenvironment. Galloflavin treatment could significantly attenuate the malignant behavior of SW480 in the inflammatory microenvironment and inhibit the migration and invasion capabilities of SW480. The knockout of NLRP3 inhibited the effect of galloflavin, which did not significantly change the migration and invasion abilities. Molecular docking and pull-down assay revealed a targeted binding relationship between galloflavin and NLRP3 and that galloflavin is bound to NLRP3 not ASC protein. Moreover, galloflavin could inhibit tumor growth and decrease the expression of NLRP in tumor-bearing mice.Conclusion: In this study, we found that NLRP3 could promote the migration and invasion of colorectal cancer cells in the inflammatory microenvironment. Galloflavin could inhibit the malignant behavior of colorectal cancer cells by targeting NLRP3.

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Curcumin inhibits epithelial-mesenchymal transition in colorectal cancer cells by regulating miR-206/SNAI2 pathway

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v18i7.6 ◽

2021 ◽

Vol 18 (7) ◽

pp. 1405-1412

Author(s):

Pan Zhao ◽

Chunjie Zhang ◽

Dafei Xie ◽

Maowei Pei

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Transition Process ◽

Cellular Migration ◽

Luciferase Assay ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Reverse Transcription Pcr ◽

Colorectal Cancer Cells

Purpose: To examine the effects of curcumin on epithelial-mesenchymal transition (EMT) via regulation of miR-206 and SNAI2 in colorectal cancer (CRC) cells. Relationship between SNAI2 and miR-206 and the effects of curcumin on related mechanisms were also identified. Methods: Transwell assays were used to analyze cellular migration and invasion. Genes associated with changes in protein and mRNA expression were evaluated by western blotting and quantitative reverse transcription PCR analyses, respectively. The relationship between SNAI2 and miR-206 was determined using a dual luciferase assay. Results: Curcumin inhibited cell metastasis, upregulated miR-206 expression, and decreased SNAI2 levels. Furthermore, miR-206 directly targeted SNAI2 and inhibited EMT via downregulation of SNAI2 expression. Curcumin inhibited EMT in CRC cells by upregulating miR-206. Conclusion: This study, for the first time, discovered the role of curcumin on epithelial-mesenchymal transition process in colorectal cancer cells by modulating miR-206/SNAI2 axis. These findings suggest that curcumin may be useful as a novel therapeutic agent to inhibit the metastasis of CRC.

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Sevoflurane inhibits the migration and invasion of colorectal cancer cells through regulating ERK/MMP-9 pathway by up-regulating miR-203

European Journal of Pharmacology ◽

10.1016/j.ejphar.2019.01.025 ◽

2019 ◽

Vol 850 ◽

pp. 43-52 ◽

Cited By ~ 11

Author(s):

Lihua Fan ◽

Yini Wu ◽

Jianping Wang ◽

Jiaqun He ◽

Xin Han

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Migration And Invasion ◽

Colorectal Cancer Cells

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Pals1 prevents Rac1-dependent colorectal cancer cell metastasis by inhibiting Arf6

Molecular Cancer ◽

10.1186/s12943-021-01354-2 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Simona Mareike Lüttgenau ◽

Christin Emming ◽

Thomas Wagner ◽

Julia Harms ◽

Justine Guske ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Migration ◽

Cancer Cells ◽

Cancer Cell ◽

Scaffolding Protein ◽

Migration And Invasion ◽

Tight Junction Formation ◽

Cell Metastasis ◽

Colorectal Cancer Cells

AbstractLoss of apical-basal polarity and downregulation of cell-cell contacts is a critical step during the pathogenesis of cancer. Both processes are regulated by the scaffolding protein Pals1, however, it is unclear whether the expression of Pals1 is affected in cancer cells and whether Pals1 is implicated in the pathogenesis of the disease.Using mRNA expression data and immunostainings of cancer specimen, we show that Pals1 is frequently downregulated in colorectal cancer, correlating with poorer survival of patients. We further found that Pals1 prevents cancer cell metastasis by controlling Rac1-dependent cell migration through inhibition of Arf6, which is independent of the canonical binding partners of Pals1. Loss of Pals1 in colorectal cancer cells results in increased Arf6 and Rac1 activity, enhanced cell migration and invasion in vitro and increased metastasis of transplanted tumor cells in mice. Thus, our data reveal a new function of Pals1 as a key inhibitor of cell migration and metastasis of colorectal cancer cells. Notably, this new function is independent of the known role of Pals1 in tight junction formation and apical-basal polarity.

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