Loss of BRG1 induces CRC cell senescence by regulating p53/p21 pathway

Wang, Guihua; Fu, Yinjia; Hu, Fang; Lan, Jinqing; Xu, Feng; Xi, Yong; Luo, Xuelai; Wang, Jing; Hu, Junbo

doi:10.1038/cddis.2017.1

Cited by 44 publications

(32 citation statements)

References 36 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported that BRG1 mutation or silence occurs in primary lung tumors and several cancers (50)(51)(52).In our previous paper, we show that loss of BRG1 induces colorectal cancer cell senescence through the p53/p21 pathway. We demonstrate that BRG1 binds to SIRT1 and interferes with SIRT1-mediated deacetylation of p53 at K382 (53). We also have a previous paper showing that the loss of BRG1 promotes colorectal cancer cell metastasis though Wnt pathway.…”

Section: Discussionsupporting

confidence: 65%

M2 Macrophage-Derived Exosomes Promote Cell Migration and Invasion in Colon Cancer

et al. 2019

Self Cite

View full text Add to dashboard Cite

Clinical and experimental evidence has shown that tumorassociated macrophages promote cancer initiation and progression. However, the macrophage-derived molecular determinants that regulate colorectal cancer metastasis have not been fully characterized. Here, we demonstrate that M2 macrophage-regulated colorectal cancer cells' migration and invasion is dependent upon M2 macrophage-derived exosomes (MDE). MDE displayed a high expression level of miR-21-5p and miR-155-5p, and MDE-mediated colorectal cancer cells' migration and invasion depended on these two miRNAs. Mechanistically, miR-21-5p and miR-155-5p were transferred to colorectal cancer cells by MDE and bound to the BRG1 coding sequence, downregulating expression of BRG1, which has been identified as a key factor promoting the colorectal cancer metastasis, yet is downregulated in metastatic colorectal cancer cells. Collectively, these findings show that M2 macrophages induce colorectal cancer cells' migration and invasion and provide significant plasticity of BRG1 expression in response to tumor microenvironments during malignant progression. This dynamic and reciprocal cross-talk between colorectal cancer cells and M2 macrophages provides a new opportunity for the treatment of metastatic colorectal cancer. Significance: These findings report a functional role for miRNA-containing exosomes derived from M2 macrophages in regulating migration and invasion of colorectal cancer cells.

show abstract

Section: Discussionsupporting

confidence: 65%

M2 Macrophage-Derived Exosomes Promote Cell Migration and Invasion in Colon Cancer

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…RT-qPCR was performed with specific primers (Qiagen; Hilden, Germany) and the SYBR-Green PCR Master Mix Kit (Takara, Japan) on the ABI 7500 System (Applied Biosystems; Foster City, CA, USA). The primers of CD44 and BRG1 were used as suggested in previous studies [24,30]. CAPDH was used for gene expression normalization.…”

Section: Real-time Quantitative Pcr (Rt-qpcr)mentioning

confidence: 99%

RUNX2 interacts with BRG1 to target CD44 for promoting invasion and migration of colorectal cancer cells

et al. 2020

View full text Add to dashboard Cite

Background Cancer stem cells (CSCs) play an important role in tumor invasion and metastasis. CD44 is the most commonly used marker of CSCs, with the potential to act as a determinant against the invasion and migration of CSCs and as the key factor in epithelial–mesenchymal transition (EMT)-like changes that occur in colorectal cancer (CRC). Runt-related transcription factor-2 (RUNX2) is a mesenchymal stem marker for cancer that is involved in stem cell biology and tumorigenesis. However, whether RUNX2 is involved in CSC and in inducing EMT-like changes in CRC remains uncertain, warranting further investigation. Methods We evaluated the role of RUNX2 in the invasion and migration of CRC cells as a promoter of CD44-induced stem cell- and EMT-like modifications. For this purpose, western blotting was employed to analyze the expression of differential proteins in CRC cells. We conducted sphere formation, wound healing, and transwell assays to investigate the biological functions of RUNX2 in CRC cells. Cellular immunofluorescence and coimmunoprecipitation (co-IP) assays were performed to study the relationship between RUNX2 and BRG1. Real-time quantitative PCR (RT-qPCR) and immunohistochemistry (IHC) were performed to analyze the expressions of RUNX2, BRG1, and CD44 in the CRC tissues. Results We found that RUNX2 could markedly induce the CRC cell sphere-forming ability and EMT. Interestingly, the RUNX2-mediated EMT in CRC cell may be associated with the activation of CD44. Furthermore, RUNX2 was found to interact with BRG1 to promote the recruitment of RUNX2 to the CD44 promoter. Conclusions Our cumulative findings suggest that RUNX2 and BRG1 can form a compact complex to regulate the transcription and expression of CD44, which has possible involvement in the invasion and migration of CRC cells.

show abstract

“…p53 increases the activation of p21 transcription, thereby facilitating cellular senescence . As a putative candidate for cancer treatment, p53/p21 signaling exerts a potent effect on senescence in various digestive system tumors, including HCC, colorectal cancer, gastric cancer and pancreatic cancer …”

Section: Introductionmentioning

confidence: 99%

circLARP4 induces cellular senescence through regulating miR‐761/RUNX3/p53/p21 signaling in hepatocellular carcinoma

Chen

Zuo

et al. 2019

Cancer Science

View full text Add to dashboard Cite

Circular RNAs (circRNAs), a novel class of non‐coding RNAs, have emerged as indispensable modulators in human malignancies. Aberrant cellular senescence is a phenotype observed in various cancers. The association of circRNAs with cellular senescence in tumors is yet to determined. Here, we investigated the role of circLARP4 in cellular senescence and cell proliferation in hepatocellular carcinoma (HCC). Downregulated circLARP4 level was observed in HCC tissues and cell lines. Low expression level of circLARP4 independently predicted poor survival outcome. Gain‐of‐function and loss‐of‐function assays demonstrated that circLARP4 suppressed HCC cell proliferation, mediated cell cycle arrest and induced senescence in vitro. Levels of p53 and p21, 2 key regulatory molecules in cellular senescence, were increased in circLARP4‐overexpressed HCC cells and decreased in circLARP4‐silenced HCC cells. In vivo experiments further confirmed the tumor‐suppressing activity of circLARP4. Further mechanistic studies showed that circLARP4 dampened HCC progression by sponging miR‐761, thereby promoting the expression level of RUNX3 and activating the downstream p53/p21 signaling. Our study revealed the role of circLARP4/miR‐761/RUNX3/p53/p21 signaling in HCC progression, providing a potential survival predictor and therapeutic candidate for HCC.

show abstract

Loss of BRG1 induces CRC cell senescence by regulating p53/p21 pathway

Cited by 44 publications

References 36 publications

M2 Macrophage-Derived Exosomes Promote Cell Migration and Invasion in Colon Cancer

M2 Macrophage-Derived Exosomes Promote Cell Migration and Invasion in Colon Cancer

RUNX2 interacts with BRG1 to target CD44 for promoting invasion and migration of colorectal cancer cells

circLARP4 induces cellular senescence through regulating miR‐761/RUNX3/p53/p21 signaling in hepatocellular carcinoma

Contact Info

Product

Resources

About