siRNA - Mediated LRP/LR knock-down reduces cellular viability of malignant melanoma cells through the activation of apoptotic caspases

Rebelo, Thalia M.; Vania, Leila; Ferreira, Eloise; Weiß, Stefan

doi:10.1016/j.yexcr.2018.04.003

Cited by 11 publications

(9 citation statements)

References 46 publications

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“…Some of these DEGs had been investigated previously, including CDK2, AKT1 and KIT [13, 14], which have been widely accepted as oncogenes in melanoma. Moreover, the PPI network analysis showed that AKT1 is located at the center of the network and is connected with multiple DEGs; other hub genes such as CDK2, KIT and CASP8 also connected with multiple genes, in agreement with the results of other studies [13, 15]. The GO and KEGG analyses showed that these DEGs are enriched in melanoma development-related pathways, for example, the KEGG pathways that are denoted pathways in cancers, PI3K–AKT signaling pathway, and Ras signaling pathway.…”

Section: Discussionsupporting

confidence: 89%

Bioinformatics-based analysis reveals elevated MFSD12 as a key promoter of cell proliferation and a potential therapeutic target in melanoma

Wei

Zhu

et al. 2018

Oncogene

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Although recent therapeutic advances based on our understanding of molecular phenomena have prolonged the survival of melanoma patients, the prognosis of melanoma remains dismal and further understanding of the underlying mechanism of melanoma progression is needed. In this study, differential expression analyses revealed that many genes, including AKT1 and CDK2, play important roles in melanoma. Functional analyses of differentially expressed genes (DEGs), obtained from the GEO (Gene Expression Omnibus) database, indicated that high proliferative and metastatic abilities are the main characteristics of melanoma and that the PI3K and MAPK pathways play essential roles in melanoma progression. Among these DEGs, major facilitator superfamily domain-containing 12 (MFSD12) was found to have significantly and specifically upregulated expression in melanoma, and elevated MFSD12 level promoted cell proliferation by promoting cell cycle progression. Mechanistically, MFSD12 upregulation was found to activate PI3K signaling, and a PI3K inhibitor reversed the increase in cell proliferation endowed by MFSD12 upregulation. Clinically, high MFSD12 expression was positively associated with shorter overall survival (OS) and disease-free survival (DFS) in melanoma patients, and MFSD12 was an independent prognostic factor for OS and DFS in melanoma patients. Therapeutically, in vivo assays further confirmed that MFSD12 interference inhibited tumor growth and lung metastasis in melanoma. In conclusion, elevated MFSD12 expression promotes melanoma cell proliferation, and MFSD12 is a valuable prognostic biomarker and promising therapeutic target in melanoma.

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Section: Discussionsupporting

confidence: 89%

Bioinformatics-based analysis reveals elevated MFSD12 as a key promoter of cell proliferation and a potential therapeutic target in melanoma

Wei

Zhu

et al. 2018

Oncogene

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“…Given their various implications in cellular regulation, it is not surprising to find elevated LAMR expression in various cancers (282)(283)(284)(285)(286)(287)(288) and their involvement in tumor cell growth, migration, invasion, and aggressiveness (266,282,289). Importantly, laminin 1-LAMR interaction was shown to be implicated in tumor cell adhesion (271,290) and invasion (291,292) and LAMR down-regulation was shown to promote tumor cell apoptosis (293)(294)(295)(296). Whether this is mediated by laminin 1-dependent activation of LAMR remains unknown.…”

Section: /67 Kda Laminin Receptors (Lamr)mentioning

confidence: 99%

Targeting the Extra-Cellular Matrix—Tumor Cell Crosstalk for Anti-Cancer Therapy: Emerging Alternatives to Integrin Inhibitors

2020

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“…LRP/LR is implicated in numerous diseases, including cancer, prion disorders, ageing and AD. LRP/LR is upregulated in multiple metastatic cancers causing increased metastasis, increased angiogenesis and the impediment of apoptosis [22][23][24][25][26][27][28][29][30][31][32][33][34]. Furthermore, LRP/LR is also involved in both cancer and ageing via a functional relationship with telomerase [35][36][37].…”

Section: Introductionmentioning

confidence: 99%

LRP::FLAG reduces phosphorylated tau levels in Alzheimer’s Disease

Cuttler

Bignoux

Otgaar

et al. 2020

Preprint

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Alzheimer's disease (AD) is characterized by amyloid beta (Aβ) plaque and neurofibrillary tangle formation, respectively. Neurofibrillary tangles form as a result of the intracellular accumulation of hyperphosphorylated tau. Telomerase activity and levels of the human reverse transcriptase (hTERT) subunit of telomerase are significantly decreased in AD. Recently it has been demonstrated that the 37kDa/67kDa laminin receptor (LRP/LR) interacts with telomerase and is implicated in Aβ pathology. Here we show that LRP/LR co-localizes with tau in the perinuclear cell compartment and FRET confirmed a direct interaction between LRP/LR and tau in HEK-293 cells. Overexpression of LRP::FLAG in HEK-293 and SH-SY5Y cells decreased total and phosphorylated tau levels with a concomitant decrease in PrP c levels, a tauopathy-related protein. Additionally, LRP::FLAG overexpression resulted in increased hTERT levels. These data indicate for the first time a role of LRP/LR in tauopathy of Alzheimer's Disease and recommend LRP::FLAG as a potential alternative therapeutic tool for Alzheimer's Disease treatment through rescuing cells from A induced cytotoxicity and, as shown in this report, decreased phosphorylated tau levels.

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siRNA - Mediated LRP/LR knock-down reduces cellular viability of malignant melanoma cells through the activation of apoptotic caspases

Cited by 11 publications

References 46 publications

Bioinformatics-based analysis reveals elevated MFSD12 as a key promoter of cell proliferation and a potential therapeutic target in melanoma

Bioinformatics-based analysis reveals elevated MFSD12 as a key promoter of cell proliferation and a potential therapeutic target in melanoma

Targeting the Extra-Cellular Matrix—Tumor Cell Crosstalk for Anti-Cancer Therapy: Emerging Alternatives to Integrin Inhibitors

LRP::FLAG reduces phosphorylated tau levels in Alzheimer’s Disease

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