The therapeutically actionable long non-coding RNA ‘T-RECS’ is essential to cancer cells’ survival in NRAS/MAPK-driven melanoma DOI Creative Commons
Valentin Feichtenschlager,

Li-Nan Chen,

Yixuan James Zheng

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 1, 2023

Abstract Finding effective therapeutic targets to treat NRAS-mutated melanoma remains a challenge. Long non-coding RNAs (lncRNAs) recently emerged as essential regulators of tumorigenesis. Using discovery approach combining experimental models and unbiased computational analysis complemented by validation in patient biospecimens, we identified nuclear-enriched lncRNA ( AC004540.4 ) that is upregulated NRAS/MAPK-dependent melanoma, named T-RECS . Considering potential innovative treatment strategies, designed antisense oligonucleotides (ASOs) target ASOs reduced the growth cells induced apoptotic cell death, while having minimal impacton normal primary melanocytes. Mechanistically, with downregulated activity pro-survival kinases protein stability hnRNPA2/B1, pro-oncogenic regulator MAPK signaling. patient- line- derived tumor xenograft mouse models, demonstrated systemic significantly suppressed tumors, no noticeable toxicity. ASO-mediated inhibition represents promising RNA-targeting improve outcome pathway-activated melanoma.

Language: Английский

Advances in Melanoma: From Genetic Insights to Therapeutic Innovations DOI Creative Commons
Fernando Valdez-Salazar,

Luis Alberto Jiménez-Del Río,

Jorge Ramón Padilla‐Gutiérrez

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(8), P. 1851 - 1851

Published: Aug. 14, 2024

Advances in melanoma research have unveiled critical insights into its genetic and molecular landscape, leading to significant therapeutic innovations. This review explores the intricate interplay between alterations, such as mutations BRAF, NRAS, KIT, pathogenesis. The MAPK PI3K/Akt/mTOR signaling pathways are highlighted for their roles tumor growth resistance mechanisms. Additionally, this delves impact of epigenetic modifications, including DNA methylation histone changes, on progression. microenvironment, characterized by immune cells, stromal soluble factors, plays a pivotal role modulating behavior treatment responses. Emerging technologies like single-cell sequencing, CRISPR-Cas9, AI-driven diagnostics transforming research, offering precise personalized approaches treatment. Immunotherapy, particularly checkpoint inhibitors mRNA vaccines, has revolutionized therapy enhancing body’s response. Despite these advances, mechanisms remain challenge, underscoring need combined therapies ongoing achieve durable comprehensive overview aims highlight current state transformative impacts advancements clinical practice.

Language: Английский

Citations

8
Molecular targeted therapies for cutaneous squamous cell carcinoma: recent developments and clinical implications. DOI
H. B. Singh, Hitesh Chopra, Inderbir Singh

et al.

PubMed, Journal Year: 2024, Volume and Issue: 23, P. 300 - 334

Published: Jan. 1, 2024

Cutaneous Squamous Cell Carcinoma (cSCC) is a common and potentially fatal type of skin cancer that poses significant threat to public health has high prevalence rate. Exposure ultraviolet radiation on the surface increases risk cSCC, especially in those with genetic syndromes like xerodermapigmentosum epidermolysis bullosa. Therefore, understanding molecular pathogenesis cSCC critical for developing personalized treatment approaches are effective cSCC. This article provides comprehensive overview current knowledge pathogenesis, emphasizing dysregulated signaling pathways significance profiling. Several limitations challenges associated conventional therapies, however, identified, stressing need novel therapeutic strategies. The further discusses targets approaches, i.e., epidermal growth factor receptor inhibitors, hedgehog pathway PI3K/AKT/mTOR as well emerging agents. manuscript explores resistance mechanisms molecularly targeted therapies proposes methods overcome them, including combination strategies, rational design, optimization. clinical implications patient outcomes molecular-targeted treatments assessed, response rates survival outcomes. management adverse events toxicities crucial requires careful monitoring control. paper future directions advancement research this area, difficulties constraints therapies.

Language: Английский

Citations

7
The therapeutically actionable long non-coding RNA ‘T-RECS’ is essential to cancer cells’ survival in NRAS/MAPK-driven melanoma DOI Creative Commons
Valentin Feichtenschlager,

Li-Nan Chen,

Yixuan James Zheng

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Feb. 22, 2024

Abstract Finding effective therapeutic targets to treat NRAS-mutated melanoma remains a challenge. Long non-coding RNAs (lncRNAs) recently emerged as essential regulators of tumorigenesis. Using discovery approach combining experimental models and unbiased computational analysis complemented by validation in patient biospecimens, we identified nuclear-enriched lncRNA ( AC004540.4 ) that is upregulated NRAS/MAPK-dependent melanoma, named T-RECS . Considering potential innovative treatment strategies, designed antisense oligonucleotides (ASOs) target ASOs reduced the growth cells induced apoptotic cell death, while having minimal impact on normal primary melanocytes. Mechanistically, with downregulated activity pro-survival kinases protein stability hnRNPA2/B1, pro-oncogenic regulator MAPK signaling. patient- line- derived tumor xenograft mouse models, demonstrated systemic significantly suppressed tumors, no noticeable toxicity. ASO-mediated inhibition represents promising RNA-targeting improve outcome pathway-activated melanoma.

Language: Английский

Citations

6
Pancreatic Neuroendocrine Tumors: Signaling Pathways and Epigenetic Regulation DOI Open Access

Zena Saleh,

Matthew C. Moccia, Zachary Ladd

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1331 - 1331

Published: Jan. 22, 2024

Pancreatic neuroendocrine tumors (PNETs) are characterized by dysregulated signaling pathways that crucial for tumor formation and progression. The efficacy of traditional therapies is limited, particularly in the treatment PNETs at an advanced stage. Epigenetic alterations profoundly impact activity cancer development, offering potential opportunities drug development. There currently a lack extensive research on epigenetic regulation PNETs. To fill this gap, we first summarize major events involved PNET Then, discuss these context both commonly occurring—and therefore more extensively studied—malignancies. Finally, will offer perspective future direction epigenome its applications patient care.

Language: Английский

Citations

4
The regulatory role and therapeutic potential of long non-coding RNA in non-small cell lung cancer DOI Creative Commons

Sunming Xia,

Xiao Lu,

W Q Wang

et al.

Journal of Cancer, Journal Year: 2025, Volume and Issue: 16(4), P. 1137 - 1148

Published: Jan. 6, 2025

Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung (NSCLC) being predominant subtype. Recent advances in transcriptome sequencing have highlighted critical role long non-coding RNAs (lncRNAs) NSCLC, lncRNAs influencing gene expression through epigenetic, transcriptional, and post-transcriptional mechanisms. Despite growing understanding lncRNAs, challenges such as delayed diagnosis drug resistance continue to complicate NSCLC management. This review explores novel findings (e.g., MALAT1, HOTAIR, GAS5) a particular focus on their encoded small peptides N6-methyladenosine (m6A) modifications. We further discuss how interplay between peptides, m6A modifications can provide new strategies for improving diagnosis, treatment, overcoming resistance. also highlights emerging research avenues that could lead innovative clinical interventions NSCLC.

Language: Английский

Citations

0
Novel Biological Strategies for Melanoma Therapy: A Focus on lncRNAs and Their Targeting DOI Open Access
Francesca Maria Orlandella, Rosaria Arcone, Neila Luciano

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(8), P. 1273 - 1273

Published: April 9, 2025

Increasing evidence revealed that restoring the correct expression of lncRNAs could have implications in management melanoma patients. In this context, here, we aim to dissect main characteristics altered and their crosstalk with signaling pathways involved progression disease. We also highlight role nucleic acid-based techniques natural compounds (i.e., phytochemicals) as a therapeutic tool increase or silence cancer cells. Finally, explore advances nanotechnologies delivery systems efficiently carry these chemicals into cells, thus limiting potential off-target effects. The analysis literature showed HOTAIR, MALAT1, H19 are oncogenic most studied melanoma, while MEG3 is an important tumor suppressor decreased cancer. aberrant affects several hallmarks cancer, e.g., proliferation, motility, epithelial mesenchymal transition, promoting plasticity drug resistance. frame, siRNA, antisense oligonucleotide, CRISPR-Cas9 genome editing appear be effective acid strategies restore physiologic lncRNA, curcumin, resveratrol, quercetin phytochemicals able target influence Overall, study provides comprehensive overview regarding phenotype cells targeting using RNA-based therapy products.

Language: Английский

Citations

0
Long noncoding RNA MALAT1 in dermatologic disorders: a comprehensive review DOI
Dayanara Ruiz-Ojeda, Carlos A. Guzmán-Martín, Rafael Bojalil

et al.

Biomarkers in Medicine, Journal Year: 2024, Volume and Issue: 18(19), P. 853 - 867

Published: July 9, 2024

Dermatologic disorders, affecting the integumentary system, involve diverse molecular mechanisms such as cell proliferation, apoptosis, inflammation and immune responses. Long noncoding RNAs, particularly Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1), are crucial regulators of gene expression. MALAT1 influences inflammatory responses, function signaling pathways, impacting various physiological pathological processes, including dermatologic disorders. Dysregulation is observed in skin conditions like psoriasis, atopic dermatitis systemic lupus erythematosus. However, its precise role remains unclear. This review consolidates knowledge on MALAT1's impact biology pathology, emphasizing potential diagnostic therapeutic implications conditions.

Language: Английский

Citations

2
LncRNAs in melanoma phenotypic plasticity: emerging targets for promising therapies DOI Creative Commons

Tonin Beatriz Cristina Biz,

Carla A. Sousa,

S. John

et al.

RNA Biology, Journal Year: 2024, Volume and Issue: 21(1), P. 81 - 93

Published: Nov. 5, 2024

Long non-coding RNAs (lncRNAs) have received growing attention due to their diverse regulatory roles in cancer, including melanoma, an aggressive type of skin cancer. The plasticity and phenotypic adaptability melanoma cells are crucial factors contributing therapeutic resistance. identification molecules playing key cell could unravel novel more effective targets. This review presents current concepts plasticity, illustrating its fluidity dismissing the outdated notion epithelial-mesenchymal-like transition as a simplistic binary process. Emphasis is placed on pivotal role lncRNAs orchestrating employing various mechanisms recently elucidated unveiling potential promising targets for strategies. Insights into molecular coordinated by pave way development RNA-based therapies, holding great promise enhancing treatment outcomes offering glimpse approach treatment.

Language: Английский

Citations

0
The therapeutically actionable long non-coding RNA ‘T-RECS’ is essential to cell survival in NRAS/MAPK-driven melanoma DOI Creative Commons
Valentin Feichtenschlager,

Li-Nan Chen,

Yixuan James Zheng

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 27, 2023

Abstract Finding effective therapeutic targets to treat NRAS-mutated melanoma remains a challenge. Long non-coding RNAs (lncRNAs) recently emerged as essential regulators of tumorigenesis. Using discovery approach combining experimental models and unbiased computational analysis complemented by validation in patient biospecimens, we identified nuclear-enriched lncRNA ( AC004540.4 ) that is upregulated NRAS/MAPK-dependent melanoma, named T-RECS . Considering potential innovative treatment strategies, designed antisense oligonucleotides (ASOs) target ASOs reduced the growth cells induced apoptotic cell death, while having minimal impacton normal primary melanocytes. Mechanistically, with downregulated activity pro-survival kinases protein stability hnRNPA2/B1, pro-oncogenic regulator MAPK signaling. patient- line- derived tumor xenograft mouse models, demonstrated systemic significantly suppressed tumors, no noticeable toxicity. ASO-mediated inhibition represents promising RNA-targeting improve outcome pathway-mutated melanoma.

Language: Английский

Citations

0
The therapeutically actionable long non-coding RNA ‘T-RECS’ is essential to cancer cells’ survival in NRAS/MAPK-driven melanoma DOI Creative Commons
Valentin Feichtenschlager,

Li-Nan Chen,

Yixuan James Zheng

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 1, 2023

Abstract Finding effective therapeutic targets to treat NRAS-mutated melanoma remains a challenge. Long non-coding RNAs (lncRNAs) recently emerged as essential regulators of tumorigenesis. Using discovery approach combining experimental models and unbiased computational analysis complemented by validation in patient biospecimens, we identified nuclear-enriched lncRNA ( AC004540.4 ) that is upregulated NRAS/MAPK-dependent melanoma, named T-RECS . Considering potential innovative treatment strategies, designed antisense oligonucleotides (ASOs) target ASOs reduced the growth cells induced apoptotic cell death, while having minimal impacton normal primary melanocytes. Mechanistically, with downregulated activity pro-survival kinases protein stability hnRNPA2/B1, pro-oncogenic regulator MAPK signaling. patient- line- derived tumor xenograft mouse models, demonstrated systemic significantly suppressed tumors, no noticeable toxicity. ASO-mediated inhibition represents promising RNA-targeting improve outcome pathway-activated melanoma.

Language: Английский

Citations

0