Quantitative Proteomics Approach to Screening of Potential Diagnostic and Therapeutic Targets for Laryngeal Carcinoma

Li, Li; Zhang, Zhenwei; Wang, Chengyu; Miao, Lei; Zhang, Jianpeng; Wang, Jiasen; Jiao, Binghua; Zhao, Song

doi:10.1371/journal.pone.0090181

Cited by 31 publications

(29 citation statements)

References 41 publications

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“…3C and SI Appendix, Fig. S4A) and notably, 6 of these genes (ARNTL, CEACAM7, GATA2, HHEX, KLRG1, and OGN) have been reported to possess tumor suppressor activity (18)(19)(20)(21)(22)(23). qPCR analysis of the 10 genes in three additional breast cancer cell lines revealed that their expression was down-regulated in hypoxia in a similar manner to that observed in MCF7 breast cancer cells (SI Appendix, Fig.…”

Section: Resultsmentioning

confidence: 59%

G9a drives hypoxia-mediated gene repression for breast cancer cell survival and tumorigenesis

Casciello

Al-Ejeh

Kelly

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

112

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G9a is an epigenetic regulator that methylates H3K9, generally causing repression of gene expression, and participates in diverse cellular functions. G9a is genetically deregulated in a variety of tumor types and can silence tumor suppressor genes and, therefore, is important for carcinogenesis. Although hypoxia is recognized to be an adverse factor in tumor growth and metastasis, the role of G9a in regulating gene expression in hypoxia has not been described extensively. Here, we show that G9a protein stability is increased in hypoxia via reduced proline hydroxylation and, hence, inefficient degradation by the proteasome. This inefficiency leads to an increase in H3K9me2 at its target promoters. Blocking the methyltransferase activity of G9a inhibited cellular proliferation and migration in vitro and tumor growth in vivo. Furthermore, an increased level of G9a is a crucial factor in mediating the hypoxic response by down-regulating the expression of specific genes, including ARNTL, CEACAM7, GATA2, HHEX, KLRG1, and OGN. This down-regulation can be rescued by a small molecule inhibitor of G9a. Based on the hypothesis that the changes in gene expression would influence patient outcomes, we have developed a prognostic G9a-suppressed gene signature that can stratify breast cancer patients. Together, our findings provide an insight into the role G9a plays as an epigenetic mediator of hypoxic response, which can be used as a diagnostic marker, and proposes G9a as a therapeutic target for solid cancers.

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Section: Resultsmentioning

confidence: 59%

G9a drives hypoxia-mediated gene repression for breast cancer cell survival and tumorigenesis

Casciello

Al-Ejeh

Kelly

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

112

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“…This study also showed a reduction or absence of OGN expression in different tumors, such as adenocarcinomas of the breast, colon, lung, ovary, prostate, and pancreas and in different cancer cell lines, where p53 is frequently mutated or inactivated (19). Moreover, many other studies have shown decreased OGN expression in different cancers, such as human gastric cancer (68), colorectal adenoma (69), squamous cervical and squamous vaginal cancer (70), invasive ductal breast carcinoma (71), laryngeal carcinoma (72), and mouse and human thyroid tumors (73), when compared to its expression in control tissues. The latter study even showed a progressive decrease in OGN expression compared with that in normal tissue, in follicular adenoma progressing to aggressive follicular adenoma, indicating that a decrease in OGN expression parallels thyroid tumor progression.…”

Section: Ogn In Diseasementioning

confidence: 99%

The diverse functions of osteoglycin: a deceitful dwarf, or a master regulator of disease?

2016

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Small leucine-rich proteoglycans are emerging as important regulatory proteins within the extracellular matrix, where they exert both structural and nonstructural functions and hence are modulators of numerous biological processes, such as inflammation, fibrosis, and cell proliferation. One proteoglycan in particular, osteoglycin (OGN), also known as mimecan, shows great structural and functional diversity in normal physiology and in disease states, therefore making it a very interesting candidate for the development of novel therapeutic strategies. Unfortunately, the literature on OGN is confusing, as it has different names, and different transcript and protein variants have been identified. This review will give a clear overview of the different structures and functions of OGN that have been identified to date, portray its central role in pathophysiology, and highlight the importance of posttranslational processing, such as glycosylation, for the diversity of its functions.-Deckx, S., Heymans, S., Papageorgiou, A.-P. The diverse functions of osteoglycin: a deceitful dwarf, or a master regulator of disease? FASEB J. 30, 2651-2661 (2016). www.fasebj.orgThe extracellular matrix is a complex network of structural and nonstructural matrix proteins with a fundamental role in development, homeostasis, and pathophysiology. Small leucine-rich proteoglycans (SLRPs) are proteoglycans present in the extracellular matrix, where they are involved in a wide range of processes such as inflammation, fibrosis, and cell proliferation (1-4). Given the diversity of SLRPs, these proteoglycans are interesting targets for matrix-related research. In particular, osteoglycin (OGN), a class III SLRP member with multiple glycosylation sites, has been shown to be involved in many physiological processes (e.g., collagen fibrillogenesis, cell proliferation, and development), and in diverse pathologic entities, such as cardiovascular disease, cancer, and eye disease. Despite extensive research on OGN, the literature is rather confusing, because different names have been used for OGN, such as osteoinductive factor or mimecan, and different transcript and protein variants have been identified. Moreover, posttranslational processing, such as glycosylation, paramount in providing diversity in structure and function, is often poorly described. Hence, an identified function of OGN is rarely annotated to a certain transcript or glycosylated protein variant, adding to the confusion. Therefore, the purpose of this review is to give a clear overview of the different structures and functions of OGN known so far, highlight the importance of its glycosylation for the diversity in function, and describe its central role during normal physiology and in different pathological conditions. OGN: A DECEITFUL DWARFSLRPs have leucine-rich repeats (LRRs) (5), which are conserved motifs that are present from bacteria to humans and are critical for many processes, such as proteinprotein interactions, signal transduction, cell adhesion, and DNA repair (5). ...

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“…Mimecan (or Osteoglycin, OGN), is a secretory protein that belongs to a family of small leucine rich proteoglycan (SLRPs). It has been found in several cancer cell lines, although its physiological function has not been completely understood [18, 19], being abundant in bone matrix, cartilage cells, and connective tissues; it is also important for collagen fibrillogenesis, cellular growth, differentiation and migration [20] and it has been involved in the pathogenesis of different cancers such as colorectal [21], laryngeal carcinoma [19] and cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

Differential proteins among normal cervix cells and cervical cancer cells with HPV-16 infection, through mass spectrometry-based Proteomics (2D-DIGE) in women from Southern México

et al. 2016

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BackgroundCervical cancer (CC) is the fourth most common cancer in women worldwide with an estimated 528,000 new cases in 2012. The same year México had an incidence of 13,960 and a mortality of 4769 cases. There are several diagnosis methods of CC; among the most frequents are the conventional Pap cytology (Pap), colposcopy, and visual inspection with acetic acid (VIA), histopathological examination, tests of imaging and detection of high-risk papilloma virus (HR-HPV) with molecular tests (PCR, hybridization, sequencing). Proteomics is a tool for the detection of new biomarkers that can be associated with clinical stage, histological type, prognosis, and/or response to treatment. In this study we performed a comparative analysis of CC cells with normal cervical cells. The proteomic analysis was carried out with the fluorescent two-dimensional electrophoresis (2D-DIGE) technique to subsequently identify differential protein profiles using Decyder Software, and the selected proteins were identified by Mass Spectrometry (MALDI-TOF).ResultsThe proteins that showed an increased expression in cervical cancer in comparison with normal cervix cells were: Mimecan, Actin from aortic smooth muscle and Lumican. While Keratin, type II cytoskeletal 5, Peroxiredoxin-1 and 14-3-3 protein sigma showed a decrease in their protein expression level in cervical cancer in comparison with normal cervix cells.ConclusionsThus, this study was successful in identifying biomarker signatures for cervical cancer, and might provide new insights into the mechanism of CC progression.

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Quantitative Proteomics Approach to Screening of Potential Diagnostic and Therapeutic Targets for Laryngeal Carcinoma

Cited by 31 publications

References 41 publications

G9a drives hypoxia-mediated gene repression for breast cancer cell survival and tumorigenesis

G9a drives hypoxia-mediated gene repression for breast cancer cell survival and tumorigenesis

The diverse functions of osteoglycin: a deceitful dwarf, or a master regulator of disease?

Differential proteins among normal cervix cells and cervical cancer cells with HPV-16 infection, through mass spectrometry-based Proteomics (2D-DIGE) in women from Southern México

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