Upregulation of OSBPL3 by HIF1A promotes colorectal cancer progression through activation of RAS signaling pathway

AbstractOxysterol-binding protein like protein 3 (OSBPL3) has been shown involving in the development of several human cancers. However, the relationship between OSBPL3 and colorectal cancer (CRC), particularly the role of OSBPL3 in the proliferation, invasion and metastasis of CRC remains unclear. In this study, we investigated the role of OSBPL3 in CRC and found that its expression was significantly higher in CRC tissues than that in normal tissues. In addition, high expression of OSBPL3 was closely related to poor differentiation, advanced TNM stage and poor prognosis of CRC. Further experiments showed that over-expression of OSBPL3 promoted the proliferation, invasion and metastasis of CRC in vitro and in vivo models. Moreover, we revealed that OSBPL3 promoted CRC progression through activation of RAS signaling pathway. Furthermore, we demonstrated that hypoxia induced factor 1 (HIF-1A) can regulate the expression of OSBPL3 via binding to the hypoxia response element (HRE) in the promoter of OSBPL3. In summary, Upregulation of OSBPL3 by HIF1A promotes colorectal cancer progression through activation of RAS signaling pathway. This novel mechanism provides a comprehensive understanding of both OSBPL3 and the RAS signaling pathway in the progression of CRC and indicates that the HIF1A–OSBPL3–RAS axis is a potential target for early therapeutic intervention in CRC progression.

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CCT8 recovers WTp53-suppressed cell cycle evolution and EMT to promote colorectal cancer progression

Oncogenesis ◽

10.1038/s41389-021-00374-3 ◽

2021 ◽

Vol 10 (12) ◽

Author(s):

Qing Liao ◽

Yun Ren ◽

Yuyi Yang ◽

Xiaohui Zhu ◽

Yunfei Zhi ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Cycle ◽

Cancer Progression ◽

Clinical Intervention ◽

Underlying Mechanism ◽

Invasion And Metastasis ◽

Colorectal Cancer Progression ◽

Chaperone Complex

AbstractLIM and SH3 protein 1 (LASP1) is a metastasis-related protein reported to enhance tumor progression in colorectal cancer (CRC). However, the underlying mechanism is still elusive. The chaperonin protein containing TCP1 (CCT) is a cellular molecular chaperone complex, which is necessary for the correct folding of many proteins. It contains eight subunits, CCT1-8. CCT8 is overexpressed in many cancers, however, studies on CCT8 are limited and its role on CRC development and progression remains elusive. In this study, we confirmed that CCT8 and LASP1 can interact with each other and express positively in CRC cells. CCT8 could recover the ability of LASP1 to promote the invasion of CRC; CCT8 could significantly promote the proliferation, invasion, and metastasis of colorectal cells in vivo and in vitro. Mechanically, CCT8 inhibited the entry of WTp53 into the nucleus, and there was a negative correlation between the expression of CCT8 and the nuclear expression of WTp53 in clinical colorectal tissues. CCT8 promoted the cell cycle evolution and EMT progression of CRC by inhibiting the entry of WTp53 into the nucleus. Clinically, CCT8 was highly expressed in CRC. More importantly, the overall survival of CRC patients with high expression of CCT8 was worse than that of patients with low expression of CCT8. These findings indicate that as LASP1-modulated proteins, CCT8 plays a key role in promoting the progression of colorectal cancer, which provides a potential target for clinical intervention in patients with colorectal cancer.

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Osteopontin as a Regulator of Colorectal Cancer Progression and Its Clinical Applications

Cancers ◽

10.3390/cancers13153793 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3793

Author(s):

Katyana Amilca-Seba ◽

Michèle Sabbah ◽

Annette K. Larsen ◽

Jérôme A. Denis

Keyword(s):

Colorectal Cancer ◽

Cancer Progression ◽

Clinical Applications ◽

Invasion And Metastasis ◽

Clinical Laboratories ◽

Clinical Biomarker ◽

Colorectal Cancer Progression ◽

Routine Assay ◽

Tumor Types

A high expression of the phosphoprotein osteopontin (OPN) has been associated with cancer progression in several tumor types, including breast cancer, hepatocarcinoma, ovarian cancer, and colorectal cancer (CRC). Interestingly, OPN is overexpressed in CRC and is associated with a poor prognosis linked to invasion and metastasis. Here, we review the regulation and functions of OPN with an emphasis on CRC. We examine how epigenetic and genetic regulators interact with the key signaling pathways involved in this disease. Then, we describe the role of OPN in cancer progression, including proliferation, survival, migration, invasion, and angiogenesis. Furthermore, we outline the interest of using OPN as a clinical biomarker, and discuss if and how osteopontin can be implemented as a routine assay in clinical laboratories for monitoring CRC patients. Finally, we discuss the use of OPN an attractive, but challenging, therapeutic target.

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APOC2 accelerates colorectal cancer progression via modulating lipid metabolism and transcriptional activity of PHF8

10.1101/680967 ◽

2019 ◽

Author(s):

Jian Chen ◽

Chao Xiao ◽

Yupeng Wang ◽

Guohe Song ◽

Xiaoliang Wang ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Cells ◽

Cancer Progression ◽

Blood Lipid ◽

Underlying Mechanism ◽

Omega 3 ◽

Invasion And Metastasis ◽

Colorectal Cancer Progression

AbstractThe apolipoproteins (APOs) are the major proteins in blood lipid transportation. Emerging evidence has demonstrated that APOs might exert important function in tumor cells, but the underlying mechanism remains inclusive. In this study, we aim to explore the relationship between APOC2 dysfunction and colorectal cancer (CRC) malignancy. By analyzing the expression of APOC2 in 507 patients with CRC, we demonstrated that the APOC2 was overexpressed and associated with poor prognosis in CRC. We then found that high levels of APOC2 resulted in proliferation, invasion and metastasis of CRC cells in vitro and in vivo. Mechanistically, we revealed that APOC2 directly interacted with FASN which resulted in decreased levels of omega-3 fatty acids and increased levels of alpha-ketoglutarate (α-KG). Both RNA-seq and ChIP-seq analysis revealed that APOC2 overexpression resulted accumulation of α-KG leads to activation on the transcriptional program of PHF8 and thereby contributed to activation on genes involved in cell proliferation, invasion and metastasis. Together, our study unveiled the oncogenic role of APOC2 in tumor cells, which sheds new light on the potential of APOC2 as a biomarker in the prognosis of CRC.

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TMEM100 Modulates TGF-β Signaling Pathway to Inhibit Colorectal Cancer Progression

Gastroenterology Research and Practice ◽

10.1155/2021/5552324 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Huixia Li ◽

Chuan Cheng ◽

Weibo You ◽

Jiujian Zheng ◽

Jie Xu ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Growth ◽

Signaling Pathway ◽

Cancer Progression ◽

Transmembrane Protein ◽

Expression Data ◽

Mrna Expression Data ◽

Colorectal Cancer Progression ◽

Inhibitor Gene

Objectives. This study investigated the functional mechanism of transmembrane protein 100 (TMEM100) as a tumor inhibitor gene in CRC cells and offered a reference for the treatment of CRC. Methods. The mRNA expression data of CRC were acquired from the TCGA database to mine differentially expressed mRNAs. The role of TMEM100 in the progression of CRC cells was evaluated by MTT, colony formation, scratch healing, and Transwell assays. The influence of TMEM100 on the TGF-β signaling pathway was detected by western blot. Results. TMEM100 was markedly lowly expressed in CRC. CRC cell growth was significantly suppressed by overexpressing TMEM100 but noticeably facilitated by silencing TMEM100. Overexpression of TMEM100 inhibited the activation of the TGF-β signaling pathway, thus inhibiting malignant progression of CRC. Conclusion. TMEM100 is lowly expressed in CRC, which can suppress CRC cell growth by regulating the TGF-β signaling pathway.

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Role of the long form leptin receptor and of the STAT3 signaling pathway in colorectal cancer progression

International Journal of Oncology ◽

10.3892/ijo.2011.1105 ◽

2011 ◽

Cited By ~ 1

Author(s):

Atsushi Nakajima

Keyword(s):

Colorectal Cancer ◽

Signaling Pathway ◽

Cancer Progression ◽

Leptin Receptor ◽

Stat3 Signaling ◽

Stat3 Signaling Pathway ◽

Long Form ◽

Colorectal Cancer Progression

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Diethyldithiocarbamate-copper complex (CuET) inhibits colorectal cancer progression via miR-16-5p and 15b-5p/ALDH1A3/PKM2 axis-mediated aerobic glycolysis pathway

Oncogenesis ◽

10.1038/s41389-020-00295-7 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Xin Huang ◽

Yichao Hou ◽

Xiaoling Weng ◽

Wenjing Pang ◽

Lidan Hou ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Progression ◽

Copper Complex ◽

Aerobic Glycolysis ◽

Active Role ◽

Downstream Effector ◽

Glycolysis Pathway ◽

Colorectal Cancer Progression

AbstractExploring novel anticancer drugs to optimize the efficacy may provide a benefit for the treatment of colorectal cancer (CRC). Disulfiram (DSF), as an antialcoholism drug, is metabolized into diethyldithiocarbamate-copper complex (CuET) in vivo, which has been reported to exert the anticancer effects on various tumors in preclinical studies. However, little is known about whether CuET plays an anti-cancer role in CRC. In this study, we found that CuET had a marked effect on suppressing CRC progression both in vitro and in vivo by reducing glucose metabolism. Mechanistically, using RNA-seq analysis, we identified ALDH1A3 as a target gene of CuET, which promoted cell viability and the capacity of clonal formation and inhibited apoptosis in CRC cells. MicroRNA (miR)-16-5p and 15b-5p were shown to synergistically regulate ALDH1A3, which was negatively correlated with both of them and inversely correlated with the survival of CRC patients. Notably, using co-immunoprecipitation followed with mass spectrometry assays, we identified PKM2 as a direct downstream effector of ALDH1A3 that stabilized PKM2 by reducing ubiquitination. Taken together, we disclose that CuET treatment plays an active role in inhibiting CRC progression via miR-16-5p and 15b-5p/ALDH1A3/PKM2 axis–mediated aerobic glycolysis pathway.

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Circ-GALNT16 Restrains Colorectal Cancer Progression by Enhancing the SUMOylation of hnRNPK

10.21203/rs.3.rs-501100/v1 ◽

2021 ◽

Author(s):

Chaofan Peng ◽

Yuqian Tan ◽

Peng Yang ◽

Kangpeng Jin ◽

Chuan Zhang ◽

...

Keyword(s):

Colorectal Cancer ◽

Dna Binding ◽

Rna Sequencing ◽

Cancer Progression ◽

Molecular Mechanisms ◽

Transcriptional Level ◽

Multiple Cancer ◽

Binding Ability ◽

Colorectal Cancer Progression

Abstract BackgroundEmerging studies have investigated circRNAs as significant regulation factors in multiple cancer progression. Nevertheless, the biological functions and underlying mechanisms of circRNAs in colorectal cancer progression remain unclear.MethodsA novel circRNA (circ-GALNT16) was identified by microarray and qRT-PCR. A series of phenotype experiments in vitro and vivo were performed to investigate the role of circ-GALNT16 in CRC. FISH, RNA pulldown assay, RIP assay, RNA sequencing, coimmunoprecipitation, and ChIP were constructed to explore the molecular mechanisms of circ-GALNT16 in colorectal cancer.ResultsCirc-GALNT16 was downregulated in colorectal cancer and negatively correlated with poor prognosis. Circ-GALNT16 suppressed the proliferation and metastasis ability of colorectal cancer in vitro and vivo. Mechanistically, circ-GALNT16 could bind to the KH3 domain of heterogeneous nuclear ribonucleoprotein K (hnRNPK), which resulted in the SUMOylation of hnRNPK. Additionally, circ-GALNT16 could enhance the hnRNPK-p53 complex by facilitating the SUMOylation of hnRNPK. Furthermore, RNA sequencing assay identified serpin family E member 1 as the target gene of circ-GALNT16 at the transcriptional level. Rescue assays revealed that circ-GALNT16 regulated the expression of Serpine1 by inhibiting the deSUMOylation of hnRNPK mediated by SUMO specific peptidase 2 and then regulating the sequence-specific DNA binding ability of the hnRNPK-p53 transcriptional complex.ConclusionsCirc-GALNT16 suppressed CRC progression via inhibiting Serpine1 expression through adjusting the sequence-specific DNA binding ability of the SENP2-mediated hnRNPK-p53 transcriptional complex and might work as a biomarker and therapeutic target for CRC.

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