COL6A1 promotes metastasis and predicts poor prognosis in patients with pancreatic cancer

Owusu-Ansah, Kwabena Gyabaah; Song, Guangyuan; Chen, Ronggao; Edoo, Muhammad Ibrahim Alhadi; Li, Jun; Chen, Bingjie; Wu, Jian; Zhou, Lin; Xie, Haiyang; Jiang, Donghai; Zheng, Shusen

doi:10.3892/ijo.2019.4825

Cited by 50 publications

(55 citation statements)

References 35 publications

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“…Fourth, PPI analysis revealed that potential synergy or interaction of nine core genes with PPEF1 contributed to the progression and prognosis of BC ( Figure 5). Among the core genes, COL6A1 can promote the metastasis of various tumors, 40,41 and COL6A2 is a cancer-driven gene with a mutation rate of more than 5% in BC. 42 ITGA5 promoted tumor invasion which was highly expressed in BC with migration, invasiveness and lung metastases.…”

Section: Dovepressmentioning

confidence: 99%

The Clinical Significance of PPEF1 as a Promising Biomarker and Its Potential Mechanism in Breast Cancer

Ye¹,

Wan²,

Li³

et al. 2020

OTT

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Background: Breast cancer (BC) is the leading cause of malignancy death in females worldwide. While intense efforts have been made to elucidate the pathogeny, the molecular mechanism of BC remains elusive. Thus, this study aimed to investigate the role of PPEF1 in the progression of BC and further explore the better clinical significance. Methods: The diagnostic and prognostic values of elevated PPEF1 expression in BC were unveiled via public databases analysis. In addition, Gene Ontology (GO), Gene Set Enrichment Analysis (GSEA) and Protein-protein interaction (PPI) analysis were performed to explore the potential functions and molecular mechanisms of PPEF1 in BC progression. Experimentally, transwell and CCK-8 assays were carried out to estimate the effects of PPEF1 on the BC metastasis. Meanwhile, the differential expressions of PPEF1 in paraffin-embedded tissues and serum samples were, respectively, analyzed by Immunohistochemical (IHC) analysis and enzyme-linked immunosorbent assay (ELISA) kit. Results: The transcriptional levels of PPEF1 were higher in BC than in normal breast tissues or adjacent normal tissues. Moreover, survival analysis revealed that higher PPEF1 expression was negatively associated with overall survival (OS), all events-free (AE-free) and metastatic recurrence-free (MR-free) survival, and further was an independent risk factor of unfavorable prognosis in BC patients. Additionally, the present study provided the first evidence that PPEF1 participated in multiple biological processes and underly signaling pathways involving in tumorigenesis and development of BC. Furthermore, PPEF1 promotes the BC progression and can be used as a noninvasive diagnostic marker. Noteworthy, the combined determination of serum PPEF1 and traditional tumor markers can enhance diagnostic accuracy thus is of vital importance in the early diagnosis of BC. Conclusion: PPEF1 exerted a tumorigenic role and involved in molecular mechanism of tumorigenesis in BC which served as a promising biomarker for prognosis and diagnosis.

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Section: Dovepressmentioning

confidence: 99%

The Clinical Significance of PPEF1 as a Promising Biomarker and Its Potential Mechanism in Breast Cancer

Ye¹,

Wan²,

Li³

et al. 2020

OTT

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“…MAP2K3 has been shown to enhance tumor progression, and the loss of MAP2K3 results in inhibition of cellular proliferation and increased response of tumor cells to chemotherapeutic drugs in vivo [5,12,13]. However, recent research has demonstrated that the loss of MAP2K3 copy number occurs in NSCLC and that MAP2K3 inhibits cell proliferation and promotes cellular senescence in hepatocellular carcinoma, breast cancer and melanoma [7,[14][15][16][17]. In this study, we demonstrated that MAP2K3 is downregulated in ESCC compared to casematched normal tissues.…”

Section: Discussionmentioning

confidence: 56%

The miR-19b-3p/MAP2K3/STAT3 Feedback Loop Regulates Cell Proliferation and Invasion in Esophageal Squamous Cell Carcinoma

Zhang¹,

Liu²,

Lu³

et al. 2020

Preprint

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Background Esophageal squamous cell carcinoma (ESCC) remains one of the most refractory malignancies worldwide. MAP2K3 has been reported to play an important role in tumor progression. However, whether MAP2K3 also affects ESCC remains to be determined. Method We used a CRISPR/Cas9 kinome screen to identify the genes related to ESCC cell survival. The MAP2K3 expression was detected in ESCC tissues by immunohistochemistry and westernblot. The function of MAP2K3 in ESCC was investigated using colony formation assay and Transwell assay in vivo and in vitro. RNA sequence was performed to verify its downstream signaling pathways. DNA binding of the gene promoter region was detected by chromatin immunoprecipitation.Result Downregulation of MAP2K3 was found in ESCC and correlated with clinically poor survival. MAP2K3 inhibited cell proliferation and invasion via the EGFR/STAT3 signaling pathway in ESCC cells. MAP2K3 suppressed STAT3 expression and activation by interacting with MDM2 to promote the ubiquitin proteasome degradation of STAT3. Furthermore, MAP2K3 was a downstream target of miR-19b-3p, which promoted ESCC tumorigenesis. STAT3 binds to the MIR19B promoter region to increase the expression of miR-19b-3p in ESCC cells. Conclusion In summary, our results demonstrated that the miR-19b-3p/MAP2K3/STAT3 feedback loop regulates tumorigenesis in ESCC and elucidate the potential of therapeutically targeting this pathway in ESCC.

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“…USH2A , a gene responsible for Usher syndrome, has been found to be mutated in our cohort demonstrating its role as tumor suppressor ( Van Wijk et al, 2004 ). Although, some other genes such as MCC1, COL6A1, and CYP11B2 are associated with different cancers such as pancreatic, colorectal, and hepatocellular carcinoma, their involvement in PCa is not yet explored ( Fukuyama et al, 2008 ; Fan et al, 2016 ; Owusu-Ansah et al, 2019 ). Previous studies, however, have reported the role of diet in PCa ( Labbé et al, 2015 ), so it will be enticing to explore if the genes mentioned above have any role in diet induced PCa.…”

Section: Resultsmentioning

confidence: 99%

A Pilot Study on the Whole Exome Sequencing of Prostate Cancer in the Indian Phenotype Reveals Distinct Polymorphisms

et al. 2020

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Prostate cancer (PCa) is the third most common cancer among men in India, and no next-generation sequencing (NGS) studies have been attempted earlier. Recent advances in NGS have heralded the discovery of biomarkers from Caucasian/European and Chinese ancestry, but not much is known about the Indian phenotype/variant of PCa. In a pilot study using the whole exome sequencing of benign/PCa patients, we identified characteristic mutations specific to the Indian sub-population. We observed a large number of mutations in DNA repair genes, viz. helicases, TP53, and BRCA besides the variants of unknown significance with a possibly damaging rare variant (rs730881069/chr19:55154172C/TR136Q) in the TNNI3 gene that has been previously reported as a semi-conservative amino acid substitution. Our pilot study attempts to bring an understanding of PCa prognosis and recurrence for the Indian phenotype.

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COL6A1 promotes metastasis and predicts poor prognosis in patients with pancreatic cancer

Cited by 50 publications

References 35 publications

<p>The Clinical Significance of <em>PPEF1</em> as a Promising Biomarker and Its Potential Mechanism in Breast Cancer</p>

<p>The Clinical Significance of <em>PPEF1</em> as a Promising Biomarker and Its Potential Mechanism in Breast Cancer</p>

The miR-19b-3p/MAP2K3/STAT3 Feedback Loop Regulates Cell Proliferation and Invasion in Esophageal Squamous Cell Carcinoma

A Pilot Study on the Whole Exome Sequencing of Prostate Cancer in the Indian Phenotype Reveals Distinct Polymorphisms

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