scholarly journals NUB1 and FAT10 Proteins as Potential Novel Biomarkers in Cancer: A Translational Perspective

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2176
Author(s):  
Maria Arshad ◽  
Nazefah Abdul Hamid ◽  
Mun Chiang Chan ◽  
Fuad Ismail ◽  
Geok Chin Tan ◽  
...  
Keyword(s):  
Disease Burden ◽  
Epithelial Mesenchymal Transition ◽  
Nuclear Antigen ◽  
Mesenchymal Transition ◽  
Damage Repair ◽  
Novel Biomarkers ◽  
Antigen Protein ◽  
Inducible Protein ◽  
Proliferating Cell ◽  
Interferon Inducible Protein

Cancer increases the global disease burden substantially, but it remains a challenge to manage it. The search for novel biomarkers is essential for risk assessment, diagnosis, prognosis, prediction of treatment response, and cancer monitoring. This paper examined NEDD8 ultimate buster-1 (NUB1) and F-adjacent transcript 10 (FAT10) proteins as novel biomarkers in cancer. This literature review is based on the search of the electronic database, PubMed. NUB1 is an interferon-inducible protein that mediates apoptotic and anti-proliferative actions in cancer, while FAT10 is a ubiquitin-like modifier that promotes cancer. The upregulated expression of both NUB1 and FAT10 has been observed in various cancers. NUB1 protein binds to FAT10 non-covalently to promote FAT10 degradation. An overexpressed FAT10 stimulates nuclear factor-kappa β, activates the inflammatory pathways, and induces the proliferation of cancer. The FAT10 protein interacts with the mitotic arrest deficient 2 protein, causing chromosomal instability and breast tumourigenesis. FAT10 binds to the proliferating cell nuclear antigen protein and inhibits the DNA damage repair response. In addition, FAT10 involves epithelial–mesenchymal transition, invasion, apoptosis, and multiplication in hepatocellular carcinoma. Our knowledge about them is still limited. There is a need to further develop NUB1 and FAT10 as novel biomarkers.

scholarly journals Mass Spectrometry-Based Proteomic Characterization of Cutaneous Melanoma Ectosomes Reveals the Presence of Cancer-Related Molecules

2020 ◽  
Vol 21 (8) ◽  
pp. 2934 ◽  
Author(s):  
Magdalena Surman ◽  
Sylwia Kędracka-Krok ◽  
Dorota Hoja-Łukowicz ◽  
Urszula Jankowska ◽  
Anna Drożdż ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Protein Content ◽  
Cell Lines ◽  
Cutaneous Melanoma ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Starting Point ◽  
Novel Biomarkers

Cutaneous melanoma (CM) is an aggressive type of skin cancer for which effective biomarkers are still needed. Recently, the protein content of extracellular vesicles (ectosomes and exosomes) became increasingly investigated in terms of its functional role in CM and as a source of novel biomarkers; however, the data concerning the proteome of CM-derived ectosomes is very limited. We used the shotgun nanoLC–MS/MS approach to the profile protein content of ectosomes from primary (WM115, WM793) and metastatic (WM266-4, WM1205Lu) CM cell lines. Additionally, the effect exerted by CM ectosomes on recipient cells was assessed in terms of cell proliferation (Alamar Blue assay) and migratory properties (wound healing assay). All cell lines secreted heterogeneous populations of ectosomes enriched in the common set of proteins. A total of 1507 unique proteins were identified, with many of them involved in cancer cell proliferation, migration, escape from apoptosis, epithelial–mesenchymal transition and angiogenesis. Isolated ectosomes increased proliferation and motility of recipient cells, likely due to the ectosomal transfer of different cancer-promoting molecules. Taken together, these results confirm the significant role of ectosomes in several biological processes leading to CM development and progression, and might be used as a starting point for further studies exploring their diagnostic and prognostic potential.

scholarly journals Interplay between miRNAs and host genes and their role in cancer

2019 ◽  
Vol 18 (4) ◽  
pp. 255-266 ◽  
Author(s):  
Baohong Liu ◽  
Yu Shyr ◽  
Jianping Cai ◽  
Qi Liu
Keyword(s):  
Tumor Suppressors ◽  
Target Genes ◽  
Epithelial Mesenchymal Transition ◽  
Fine Tuning ◽  
Data Sets ◽  
Protein Coding ◽  
Mesenchymal Transition ◽  
Damage Repair ◽  
Cancer Types ◽  
Host Genes

Abstract MicroRNAs (miRNAs) are small endogenous non-coding functional RNAs that post-transcriptionally regulate gene expression. They play essential roles in nearly all biological processes including cell development and differentiation, DNA damage repair, cell death as well as intercellular communication. They are highly involved in cancer, acting as tumor suppressors and/or promoters to modulate cell proliferation, epithelial-mesenchymal transition and tumor invasion and metastasis. Recent studies have shown that more than half of miRNAs are located within protein-coding or non-coding genes. Intragenic miRNAs and their host genes either share the promoter or have independent transcription. Meanwhile, miRNAs work as partners or antagonists of their host genes by fine-tuning their target genes functionally associated with host genes. This review outlined the complicated relationship between intragenic miRNAs and host genes. Focusing on miRNAs known as oncogenes or tumor suppressors in specific cancer types, it studied co-expression relationships between these miRNAs and host genes in the cancer types using TCGA data sets, which validated previous findings and revealed common, tumor-specific and even subtype-specific patterns. These observations will help understand the function of intragenic miRNAs and further develop miRNA therapeutics in cancer.

scholarly journals Increased Expressions of Matrix Metalloproteinases (MMPs) in Prostate Cancer Tissues of Men with Type 2 Diabetes

Biomedicines ◽  
2020 ◽  
Vol 8 (11) ◽  
pp. 507
Author(s):  
Andras Franko ◽  
Lucia Berti ◽  
Jörg Hennenlotter ◽  
Steffen Rausch ◽  
Marcus O. Scharpf ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Type 2 Diabetes ◽  
Matrix Metalloproteinases ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Prostate Tissue ◽  
Nuclear Antigen ◽  
Gene Expressions ◽  
Mesenchymal Transition

Type 2 diabetes (T2D) is associated with worse prognosis of prostate cancer (PCa). The molecular mechanisms behind this association are still not fully understood. The aim of this study was to identify key factors, which contribute to the more aggressive PCa phenotype in patients with concurrent T2D. Therefore, we investigated benign and PCa tissue of PCa patients with and without diabetes using real time qPCR. Compared to patients without diabetes, patients with T2D showed a decreased E-cadherin/N-cadherin (CDH1/CDH2) ratio in prostate tissue, indicating a switch of epithelial-mesenchymal transition (EMT), which is a pivotal process in carcinogenesis. In addition, the gene expression levels of matrix metalloproteinases (MMPs) and CC chemokine ligands (CCLs) were higher in prostate samples of T2D patients. Next, prostate adenocarcinoma PC3 cells were treated with increasing glucose concentrations to replicate hyperglycemia in vitro. In these cells, high glucose induced expressions of MMPs and CCLs, which showed significant positive associations with the proliferation marker proliferating cell nuclear antigen (PCNA). These results indicate that in prostate tissue of men with T2D, hyperglycemia may induce EMT, increase MMP and CCL gene expressions, which in turn activate invasion and inflammatory processes accelerating the progression of PCa.

scholarly journals The Effects of Platelet-Rich and Platelet-Poor Plasma on Biological Characteristics of BM-MSCs In Vitro

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Jiahui Zhang ◽  
Jun Zhang ◽  
Nannan Zhang ◽  
Tao Li ◽  
Xiaohe Zhou ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Platelet Rich Plasma ◽  
Biological Marker ◽  
Marker Genes ◽  
Migration Ability ◽  
Mesenchymal Transition ◽  
Platelet Poor Plasma ◽  
Pluripotency Marker ◽  
Damage Repair

Platelet-rich plasma (PRP) and its byproduct platelet-poor plasma (PPP) are rich sources of cytokines in tissue damage repair. Bone marrow-derived mesenchymal stem cells (BM-MSCs) have received more and more attention for their ability to treat multiple diseases. The purpose of our study was to investigate the biologic action of PPP and PRP on BM-MSCs. The adipogenic potential of BM-MSCs revealed no obvious change, but the osteogenic ability of BM-MSCs was enhanced after treated with PRP. CCK8 assays and cell colony formation assays showed that PRP promoted cell proliferation, while this effect of PPP was not obvious. No obvious difference was found in cell cycle and apoptosis of BM-MSCs between PRP and PPP treatment. Expression of β-galactosidase, a biological marker of senescence, was decreased upon PRP treatment which indicated that PRP provided significant protection against cellular senescence. The migratory capacity of BM-MSCs was detected by scratch and transwell assays. The results indicated that PRP could affect the migration ability of BM-MSCs. From immunofluorescence detection and western blot, we demonstrated that the level of epithelial-mesenchymal transition-related proteins was changed and several pluripotency marker genes, including Sox2, Sall4, Oct4, and Nanog, were increased. Finally, the expression of the key signal pathway such as PI3K/AKT was examined. Our findings suggested that PRP promoted cell migration of BM-MSCs via stimulating the signaling pathway of PI3K/AKT.

scholarly journals Multifaceted Roles of TRIM Proteins in Colorectal Carcinoma

2020 ◽  
Vol 21 (20) ◽  
pp. 7532
Author(s):  
Wolfgang Eberhardt ◽  
Kristina Haeussler ◽  
Usman Nasrullah ◽  
Josef Pfeilschifter
Keyword(s):  
Signaling Pathways ◽  
Epithelial Mesenchymal Transition ◽  
Biological Activities ◽  
Cell Cycle Control ◽  
Gene Mutations ◽  
Oncogenic Signaling ◽  
Mesenchymal Transition ◽  
Novel Biomarkers ◽  
Trim Proteins ◽  
Oncogenic Signaling Pathways

Colorectal cancer (CRC) is one of the most frequently diagnosed tumor in humans and one of the most common causes of cancer-related death worldwide. The pathogenesis of CRC follows a multistage process which together with somatic gene mutations is mainly attributed to the dysregulation of signaling pathways critically involved in the maintenance of homeostasis of epithelial integrity in the intestine. A growing number of studies has highlighted the critical impact of members of the tripartite motif (TRIM) protein family on most types of human malignancies including CRC. In accordance, abundant expression of many TRIM proteins has been observed in CRC tissues and is frequently correlating with poor survival of patients. Notably, some TRIM members can act as tumor suppressors depending on the context and the type of cancer which has been assessed. Mechanistically, most cancer-related TRIMs have a critical impact on cell cycle control, apoptosis, epithelial–mesenchymal transition (EMT), metastasis, and inflammation mainly through directly interfering with diverse oncogenic signaling pathways. In addition, some recent publications have emphasized the emerging role of some TRIM members to act as transcription factors and RNA-stabilizing factors thus adding a further level of complexity to the pleiotropic biological activities of TRIM proteins. The current review focuses on oncogenic signaling processes targeted by different TRIMs and their particular role in the development of CRC. A better understanding of the crosstalk of TRIMs with these signaling pathways relevant for CRC development is an important prerequisite for the validation of TRIM proteins as novel biomarkers and as potential targets of future therapies for CRC.

scholarly journals CENPK Interacts with SOX6 to Promote Cervical Cancer Stemness and Chemoresistance Through Wnt and P53 Signaling

2021 ◽  
Author(s):  
Xian Lin ◽  
Feng Wang ◽  
Jing Liu ◽  
Yibin Lin ◽  
Li Li ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Dna Damage ◽  
Wnt Signaling ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Recurrence ◽  
Cancer Stemness ◽  
Mesenchymal Transition ◽  
P53 Signaling ◽  
Damage Repair

Abstract Background Stemness and chemoresistance contribute to cervical cancer recurrence and metastasis. It is meaningful to develop alternative targets for eliminating cancer stem cells (CSCs) properties, suppressing metastasis, and alleviating chemoresistance in cervical cancer. This study clarifies the role of CENPK in cervical cancer stemness and chemoresistance and its clinical significance in cancer progression. Methods Human cervical cancer cell lines, xenografts, and clinical samples were used for expression and functional analysis. CENPK expression in cervical cancer was analyzed by bioinformatics based on a microarray and TCGA database and immunohistochemistry based on 119 paraffin-embedded cervical cancer specimens and 35 paraffin-embedded adjacent normal tissues in a tissue chip. Results CENPK served as an oncogene by promoting CSCs properties, DNA damage repair, epithelial-mesenchymal transition and DNA replication, thus inducing cisplatin/carboplatin resistance, cell metastasis and proliferation in cervical cancer. Intriguingly, targeting CENPK markedly prolonged the survival time of cervical cancer-bearing mice, and improved chemotherapy sensitivity of cervical cancer cells in vivo. CENPK also interacted with tumor suppressor gene SOX6 to activate Wnt signaling and inactivate p53 signaling. CENPK modulated expression of key regulators in CSCs properties, DNA damage repair, epithelial-mesenchymal transition and DNA replication by disrupting SOX6-β-catenin interaction, promoting β-catenin expression and nuclear translocation, and facilitating SOX6-mediated p53 ubiquitination and nuclear export, thus stimulating cervical cancer stemness, chemoresistance, metastasis and proliferation by. Interestingly, the RAD21/SMC3 complex, downstream targets of β-catenin, enhanced CENPK transcription to form a positive regulatory circuit through Wnt signaling. Facilitation of Wnt signaling by iRhom2 further activated the CENPK/SOX6-β-catenin-RAD21/SMC3 loop and conferred cervical cancer progression, suggesting a Wnt-p53 pathway crosstalk. Importantly, CENPK was upregulated in cervical cancer, correlated with cancer recurrence, and independently predicted poor patient prognosis. Conclusions This work identifies CENPK as a prognostic indicator and highlights targeting of CENPK as a novel strategy in the treatment of cervical cancer.

scholarly journals Research Progress on the Functions and Mechanism of circRNA in Cisplatin Resistance in Tumors

2021 ◽  
Vol 12 ◽  
Author(s):  
Qingchun Mu ◽  
Yue Lv ◽  
Chunmei Luo ◽  
Xiaojing Liu ◽  
Chunming Huang ◽  
...  
Keyword(s):  
Target Gene ◽  
Cisplatin Resistance ◽  
Epithelial Mesenchymal Transition ◽  
Research Progress ◽  
Circular Rnas ◽  
Overall Survival Rate ◽  
Chemotherapeutic Drug ◽  
Mesenchymal Transition ◽  
Damage Repair ◽  
Promising Target

Cisplatin is a common chemotherapeutic drug that has been used to treat of numerous tumors, including testicular, lung, bladder, ovarian, liver and head and neck cancers. Although clinical chemotherapy based on cisplatin has shown a remarkable therapeutic effect, the resistance to cisplatin becomes increasingly obvious as a patient uses it for a prolonged period. It not only affects the prognosis of these tumors, but also causes the recurrence of cancer and decreases the overall survival rate. The development of cisplatin resistance involves several mechanisms, including DNA damage repair, ATP-binding cassette (ABC) transporter, autophagy, cancer stem cells (CSCs), epithelial–mesenchymal transition (EMT), and other related signaling pathways. Interestingly, these mechanisms have been found to be influenced by circular RNAs (circRNAs) to regulate tumor proliferation, invasion, chemosensitivity, and other biological behaviors in the tumor microenvironment (TME). In recent years, circRNAs in cisplatin resistance in tumors, especially lung cancer and gastric cancer, have gradually drawn peoples’ attention. This review summarizes recent studies on the functions and mechanisms of circRNAs in cisplatin resistance. We emphasize that circRNA can be used as a promising target gene to improve drug resistance and therapeutic efficacy.

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