COL4A1 promotes the growth and metastasis of hepatocellular carcinoma cells by activating FAK-Src signaling

Wang, Ting; Jin, Haojie; Hu, Jun; Ran, Haoyu; Xu, Haoping; Wei, Lin; Gu, Jianren; Qin, Wenxin; Luo, Xiaoying; Hao, Yue

doi:10.21203/rs.3.rs-20811/v1

Cited by 10 publications

(21 citation statements)

References 43 publications

(53 reference statements)

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“…The results indicated that the expression levels of COL4A1 in glioma tissues were significantly higher than those in normal brain tissues. This is supported by previous reports that COL4A1 expression is increased in malignant tumors (16,24,25,28). For instance, COL4A1 expression is also increased in numerous types of malignant tumor tissue (such as esophageal squamous cell carcinoma, renal cell carcinoma, urothelial carcinoma of the bladder and breast cancer) and has an important impact on the occurrence and development of cancer (16,20,24,28).…”

Section: Discussionsupporting

confidence: 86%

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COL4A1 as a novel oncogene associated with the clinical characteristics of malignancy predicts poor prognosis in glioma

Wang

Liu

et al. 2021

Exp Ther Med

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Studies have indicated that collagen α-1 (IV) chain (COL4A1) has an indispensable regulatory role in the complex pathological mechanisms of numerous types of malignant tumor. However, its role in the development of glioma has remained elusive. Therefore, the present study sought to determine the association between the expression levels of COL4A1 and the clinical characteristics of gliomas by analyzing large samples. First, analysis of thousands of glioma tissue samples collected from the Gene expression profiling interactive analysis, Gene Expression Omnibus database, the Ivy glioblastoma atlas, The Human Protein Atlas, Chinese Glioma Genome Atlas and The Cancer Genome Atlas. In addition, glioma tissues and normal brain tissues from patients with glioma and epilepsy undergoing surgical resection were collected. These samples, which were subjected to a variety of different detection techniques (including sequencing data, chip data, reverse transcription-quantitative PCR, cell lines and tissue samples, in situ hybridization and immunology) revealed that COL4A1 expression was not only increased at the mRNA level but also at the protein level as compared with that in normal brain tissue. Furthermore, Kaplan-Meier analysis revealed that COL4A1 expression was associated with reduced overall survival of patients, particularly those with World Health Organization grade III glioma. Receiver operating characteristic analysis suggested that COL4A1 had a moderate diagnostic value for glioma. In addition, the Mann-Whitney U-test or Kruskal-Wallis test indicated that the expression levels of COL4A1 were positively associated with the histological type and historical grade of the tumor, patient age, 'Primary, Recurrent, Secondary' type and the chemotherapy status, and negatively associated with isocitrate dehydrogenase mutation and 1p19q co-deletion (P<0.001). Gene-set enrichment analysis indicated that overexpression of COL4A1 promoted cancer-associated pathways, such as the JAK/STAT signaling pathway and cell cycle regulation. Finally, an MTT assay, immunohistochemical analysis of the cell cycle regulator KI67 and a wound-healing assay further confirmed that knockdown of COL4A1 inhibited the proliferation and migration ability of glioma cells. In conclusion, COL4A1, as a novel oncogene, is a marker for poor prognosis in patients with glioma. The present study expanded the understanding of the pathogenesis of glioma and identified COL4A1 as a potential target for the diagnosis and treatment of gliomas.

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Section: Discussionsupporting

confidence: 86%

“…Various studies have indicated that COL4A1 is involved in the pathological process of a variety of cancer types and has a key role in their occurrence, development and metastasis (24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%

COL4A1 as a novel oncogene associated with the clinical characteristics of malignancy predicts poor prognosis in glioma

Wang

Liu

et al. 2021

Exp Ther Med

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“…41,42 On top of this, the high expression of COL4A1 promotes proliferation, invasion, and migration in hepatocellular carcinoma (HCC) via activation of FAK-Src signaling. 43 Collagen alpha-2(I) chain is a protein encoded by the COL1A2 gene, which is the bulk significantly rich form of collagen in humans. At the same time, numerous studies have revealed that COL1A2 is closely related to cancers.…”

Section: Discussionmentioning

confidence: 99%

Predicting functional circular RNA-based competitive endogenous RNA network in gastric carcinoma using novel bioinformatics analysis

Zhu

Huang

2021

Exp Biol Med (Maywood)

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Gastric cancer (GC) remains one of the most prevalent types of malignancies worldwide, and also one of the most reported lethal tumor-related diseases. Circular RNAs (circRNAs) have been certified to be trapped in multiple aspects of GC pathogenesis. Yet, the mechanism of this regulation is mostly undefined. This research is designed to discover the vital circRNA-microRNA (miRNA)-messenger RNA (mRNA) regulatory network in GC. Expression profiles with diverse levels including circRNAs, miRNAs, and mRNAs were all determined using microarray public datasets from Gene Expression Ominous (GEO). The differential circRNAs expressions were recognized against the published robust rank aggregation algorithm. Besides, a circRNA-based competitive endogenous RNA (ceRNA) interaction network was visualized via Cytoscape software (version 3.8.0). Functional and pathway enrichment analysis associated with differentially expressed targeted mRNAs were conducted using Cytoscape and an online bioinformatics database. Furthermore, an interconnected protein–protein interaction association network which consisted of 51 mRNAs was predicted, and hub genes were screened using STRING and CytoHubba. Then, several hub genes were chosen to explore their expression associated with survival rate and clinical stage in GEPIA and Kaplan-Meier Plotter databases. Finally, a carefully designed circRNA-related ceRNA regulatory subnetwork including four circRNAs, six miRNAs, and eight key hub genes was structured using the online bioinformatics tool.

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“…COL4A1 may play a critical function in the proliferation and colony formation of breast cancer cells. In particular, recent experimental results indicated that silencing COL4A1 expression in hepatocellular carcinoma HepG2 cells significantly inhibited the capacity for proliferation, migration and invasion [37]. Inhibition of COL4A2 gene expression in hepatocellular carcinoma cells attenuated the proliferation and migration ability of hepatocellular carcinoma cells [37].…”

Section: Discussionmentioning

confidence: 99%

“…In particular, recent experimental results indicated that silencing COL4A1 expression in hepatocellular carcinoma HepG2 cells significantly inhibited the capacity for proliferation, migration and invasion [37]. Inhibition of COL4A2 gene expression in hepatocellular carcinoma cells attenuated the proliferation and migration ability of hepatocellular carcinoma cells [37]. COL4A2 can be regarded as a core gene in the pathogenesis of breast cancer and has a prognostic value in breast cancer [38].…”

Section: Discussionmentioning

confidence: 99%

Integrate analysis of the prognostic values of COL4As to human gastric cancer

Zheng¹,

Chen²,

Liu³

et al. 2021

Preprint

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Collagen type IV (Col IV) is the main constituent of the basement membrane. Under physiological conditions, Col IV plays an important role in maintaining epithelial integrity and stabilizing epithelial function of the gastric mucosa. Under pathological conditions, Col IV can be free from the basement membrane under the influence of tumor cells and play a pro-metastatic role. Although there is a increasing number of investigations on Col IV, no studies to date have directly uncovered the prognostic role and potential regulatory role of the six isoforms of Col IV in gastric cancer. In the present experiment, we aimed to analyze the role of COL4A family genes in gastric cancer. COL4A1/2/3/4 was significantly overexpressed, while COL4A5/6 was decreased in gastric cancer tissues according to TCGA data and our immunohistochemical staining results. And COL4A1 had a positive correlation with tumor stage, while COL4A5/6 had negative correlations with tumor stage. COL4A1/2/4/5/6 can be considered as a diagnostic indicator of gastric cancer. High levels of COL4A1/2/4/5/6 expression may be predictive of a poor prognosis of gastric cancer. The percentages of genetic alterations in COL4As for stomach cancer varied from 3 to 17% based on the TCGA data (COL4A1, 10%; COL4A2, 8%; COL4A3, 3%; COL4A4, 5%; COL4A5, 17%; COL4A6, 17%). Besides, COL4As may modulate tumor progression by participating in classical cancer pathways: COL4A1/2/3/4/5/6 can activate the EMT process; COL4A2/3/4/6 can inhibit apoptosis and cell cycle; COL4A3/4/5 can activate the PI3K/AKT signaling pathway. This study implied that COL4As have diagnostic and prognostic value for gastric cancer.

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COL4A1 promotes the growth and metastasis of hepatocellular carcinoma cells by activating FAK-Src signaling

Cited by 10 publications

References 43 publications

COL4A1 as a novel oncogene associated with the clinical characteristics of malignancy predicts poor prognosis in glioma

COL4A1 as a novel oncogene associated with the clinical characteristics of malignancy predicts poor prognosis in glioma

Predicting functional circular RNA-based competitive endogenous RNA network in gastric carcinoma using novel bioinformatics analysis

Integrate analysis of the prognostic values of COL4As to human gastric cancer

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