scholarly journals SFPQ promotes an oncogenic transcriptomic state in melanoma

Oncogene ◽  
2021 ◽  
Author(s):  
O. Bi ◽  
C. A. Anene ◽  
J. Nsengimana ◽  
M. Shelton ◽  
W. Roberts ◽  
...  
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Primary Melanoma ◽  
Melanoma Cells ◽  
Protein Splicing ◽  
Multifunctional Protein ◽  
Mesenchymal Transition ◽  
Elevated Expression ◽  
Efficient Expression ◽  
Non Coding Rnas ◽  
Cell Phenotypes

AbstractThe multifunctional protein, splicing factor, proline- and glutamine-rich (SFPQ) has been implicated in numerous cancers often due to interaction with coding and non-coding RNAs, however, its role in melanoma remains unclear. We report that knockdown of SFPQ expression in melanoma cells decelerates several cancer-associated cell phenotypes, including cell growth, migration, epithelial to mesenchymal transition, apoptosis, and glycolysis. RIP-seq analysis revealed that the SFPQ-RNA interactome is reprogrammed in melanoma cells and specifically enriched with key melanoma-associated coding and long non-coding transcripts, including SOX10, AMIGO2 and LINC00511 and in most cases SFPQ is required for the efficient expression of these genes. Functional analysis of two SFPQ-enriched lncRNA, LINC00511 and LINC01234, demonstrated that these genes independently contribute to the melanoma phenotype and a more detailed analysis of LINC00511 indicated that this occurs in part via modulation of the miR-625-5p/PKM2 axis. Importantly, analysis of a large clinical cohort revealed that elevated expression of SFPQ in primary melanoma tumours may have utility as a prognostic biomarker. Together, these data suggest that SFPQ is an important driver of melanoma, likely due to SFPQ–RNA interactions promoting the expression of numerous oncogenic transcripts.

scholarly journals From Proteomic Mapping to Invasion-Metastasis-Cascade Systemic Biomarkering and Targeted Drugging of Mutant BRAF-Dependent Human Cutaneous Melanomagenesis

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2024
Author(s):  
Aikaterini F. Giannopoulou ◽  
Athanassios D. Velentzas ◽  
Athanasios K. Anagnostopoulos ◽  
Adamantia Agalou ◽  
Nikos C. Papandreou ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Epithelial To Mesenchymal Transition ◽  
Hypoxia Inducible Factor ◽  
Primary Melanoma ◽  
Melanoma Cells ◽  
Mesenchymal Transition ◽  
Mesenchymal To Epithelial Transition ◽  
Liquid Chromatography Tandem Mass ◽  
Novel Biomarkers

Melanoma is classified among the most notoriously aggressive human cancers. Despite the recent progress, due to its propensity for metastasis and resistance to therapy, novel biomarkers and oncogenic molecular drivers need to be promptly identified for metastatic melanoma. Hence, by employing nano liquid chromatography-tandem mass spectrometry deep proteomics technology, advanced bioinformatics algorithms, immunofluorescence, western blotting, wound healing protocols, molecular modeling programs, and MTT assays, we comparatively examined the respective proteomic contents of WM115 primary (n = 3955 proteins) and WM266-4 metastatic (n = 6681 proteins) melanoma cells. It proved that WM115 and WM266-4 cells have engaged hybrid epithelial-to-mesenchymal transition/mesenchymal-to-epithelial transition states, with TGF-β controlling their motility in vitro. They are characterized by different signatures of SOX-dependent neural crest-like stemness and distinct architectures of the cytoskeleton network. Multiple signaling pathways have already been activated from the primary melanoma stage, whereas HIF1α, the major hypoxia-inducible factor, can be exclusively observed in metastatic melanoma cells. Invasion-metastasis cascade-specific sub-routines of activated Caspase-3-triggered apoptosis and LC3B-II-dependent constitutive autophagy were also unveiled. Importantly, WM115 and WM266-4 cells exhibited diverse drug response profiles, with epirubicin holding considerable promise as a beneficial drug for metastatic melanoma clinical management. It is the proteome navigation that enables systemic biomarkering and targeted drugging to open new therapeutic windows for advanced disease.

scholarly journals Molecular Classification and Tumor Microenvironment Characterization of Gallbladder Cancer by Comprehensive Genomic and Transcriptomic Analysis

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 733
Author(s):  
Nobutaka Ebata ◽  
Masashi Fujita ◽  
Shota Sasagawa ◽  
Kazuhiro Maejima ◽  
Yuki Okawa ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Gallbladder Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
Molecular Classification ◽  
Mesenchymal Transition ◽  
Elevated Expression ◽  
Fresh Frozen ◽  
Therapeutic Decision Making

Gallbladder cancer (GBC), a rare but lethal disease, is often diagnosed at advanced stages. So far, molecular characterization of GBC is insufficient, and a comprehensive molecular portrait is warranted to uncover new targets and classify GBC. We performed a transcriptome analysis of both coding and non-coding RNAs from 36 GBC fresh-frozen samples. The results were integrated with those of comprehensive mutation profiling based on whole-genome or exome sequencing. The clustering analysis of RNA-seq data facilitated the classification of GBCs into two subclasses, characterized by high or low expression levels of TME (tumor microenvironment) genes. A correlation was observed between gene expression and pathological immunostaining. TME-rich tumors showed significantly poor prognosis and higher recurrence rate than TME-poor tumors. TME-rich tumors showed overexpression of genes involved in epithelial-to-mesenchymal transition (EMT) and inflammation or immune suppression, which was validated by immunostaining. One non-coding RNA, miR125B1, exhibited elevated expression in stroma-rich tumors, and miR125B1 knockout in GBC cell lines decreased its invasion ability and altered the EMT pathway. Mutation profiles revealed TP53 (47%) as the most commonly mutated gene, followed by ELF3 (13%) and ARID1A (11%). Mutations of ARID1A, ERBB3, and the genes related to the TGF-β signaling pathway were enriched in TME-rich tumors. This comprehensive analysis demonstrated that TME, EMT, and TGF-β pathway alterations are the main drivers of GBC and provides a new classification of GBCs that may be useful for therapeutic decision-making.

scholarly journals Bornyl cis-4-Hydroxycinnamate Suppresses Cell Metastasis of Melanoma through FAK/PI3K/Akt/mTOR and MAPK Signaling Pathways and Inhibition of the Epithelial-to-Mesenchymal Transition

2018 ◽  
Vol 19 (8) ◽  
pp. 2152 ◽  
Author(s):  
Tzu-Yen Yang ◽  
Mei-Li Wu ◽  
Chi-I Chang ◽  
Chih-I Liu ◽  
Te-Chih Cheng ◽  
...  
Keyword(s):  
Cell Migration ◽  
Signaling Pathways ◽  
Melanoma Cell ◽  
Epithelial To Mesenchymal Transition ◽  
Melanoma Cells ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Cell Migration And Invasion ◽  
Cell Metastasis ◽  
A375 Melanoma

Bornyl cis-4-hydroxycinnamate, a bioactive compound isolated from Piper betle stems, has the potential for use as an anti-cancer agent. This study investigated the effects of bornyl cis-4-hydroxycinnamate on cell migration and invasion in melanoma cells. Cell migration and invasion were compared in A2058 and A375 melanoma cell lines treated with/without bornyl cis-4-hydroxycinnamate (1–6 µM). To examine whether bornyl cis-4-hydroxycinnamate has a potential anti-metastatic effect on melanoma cells, cell migration and invasion assays were performed using a Boyden chamber assay and a transwell chamber in A2058 and A375 cells. Gelatin zymography was employed to determine the enzyme activities of MMP-2 and MMP-9. Cell lysates were collected for Western blotting analysis of matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitors of metalloproteinase-1/2 (TIMP-1/2), as well as key molecules in the mitogen-activated protein kinase (MAPK), focal adhesion kinase (FAK)/ phosphatidylinositide-3 kinases (PI3K)/Akt/ mammalian target of rapamycin (mTOR), growth factor receptor-bound protein 2 (GRB2) signaling pathways. Our results demonstrated that bornyl cis-4-hydroxycinnamate is a potentially useful agent that inhibits melanoma cell migration and invasion, and altered melanoma cell metastasis by reducing MMP-2 and MMP-9 expression through inhibition of the FAK/PI3K/Akt/mTOR, MAPK, and GRB2 signaling pathways. Moreover, bornyl cis-4-hydroxycinnamate inhibited the process of the epithelial-to-mesenchymal transition in A2058 and A375 melanoma cells. These findings suggested that bornyl cis-4-hydroxycinnamate has potential as a chemotherapeutic agent, and warrants further investigation for its use in the management of human melanoma.

scholarly journals miR-205: A Potential Biomedicine for Cancer Therapy

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1957
Author(s):  
Neeraj Chauhan ◽  
Anupam Dhasmana ◽  
Meena Jaggi ◽  
Subhash C. Chauhan ◽  
Murali M. Yallapu
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressors ◽  
Gene Network ◽  
Tumor Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Dual Nature ◽  
Mesenchymal Transition ◽  
Research Article ◽  
Drug Treatments ◽  
Non Coding Rnas

microRNAs (miRNAs) are a class of small non-coding RNAs that regulate the expression of their target mRNAs post transcriptionally. miRNAs are known to regulate not just a gene but the whole gene network (signaling pathways). Accumulating evidence(s) suggests that miRNAs can work either as oncogenes or tumor suppressors, but some miRNAs have a dual nature since they can act as both. miRNA 205 (miR-205) is one such highly conserved miRNA that can act as both, oncomiRNA and tumor suppressor. However, most reports confirm its emerging role as a tumor suppressor in many cancers. This review focuses on the downregulated expression of miR-205 and discusses its dysregulation in breast, prostate, skin, liver, gliomas, pancreatic, colorectal and renal cancers. This review also confers its role in tumor initiation, progression, cell proliferation, epithelial to mesenchymal transition, and tumor metastasis. Restoration of miR-205 makes cells more sensitive to drug treatments and mitigates drug resistance. Additionally, the importance of miR-205 in chemosensitization and its utilization as potential biomedicine and nanotherapy is described. Together, this review research article sheds a light on its application as a diagnostic and therapeutic marker, and as a biomedicine in cancer.

scholarly journals Interplay among SNAIL Transcription Factor, MicroRNAs, Long Non-Coding RNAs, and Circular RNAs in the Regulation of Tumor Growth and Metastasis

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 209 ◽  
Author(s):  
Klaudia Skrzypek ◽  
Marcin Majka
Keyword(s):  
Transcription Factor ◽  
Tumor Growth ◽  
Epithelial To Mesenchymal Transition ◽  
Cell Metabolism ◽  
Circular Rnas ◽  
Mesenchymal Transition ◽  
Expression Of Genes ◽  
Non Coding Rnas ◽  
Tumor Growth And Metastasis ◽  
Novel Therapeutic Strategies

SNAIL (SNAI1) is a zinc finger transcription factor that binds to E-box sequences and regulates the expression of genes. It usually acts as a gene repressor, but it may also activate the expression of genes. SNAIL plays a key role in the regulation of epithelial to mesenchymal transition, which is the main mechanism responsible for the progression and metastasis of epithelial tumors. Nevertheless, it also regulates different processes that are responsible for tumor growth, such as the activity of cancer stem cells, the control of cell metabolism, and the regulation of differentiation. Different proteins and microRNAs may regulate the SNAIL level, and SNAIL may be an important regulator of microRNA expression as well. The interplay among SNAIL, microRNAs, long non-coding RNAs, and circular RNAs is a key event in the regulation of tumor growth and metastasis. This review for the first time discusses different types of regulation between SNAIL and non-coding RNAs with a focus on feedback loops and the role of competitive RNA. Understanding these mechanisms may help develop novel therapeutic strategies against cancer based on microRNAs.

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