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Compositions comprising intermediate non-coding RNA regulators modulating the expression of etv6 or foxo1 and uses thereof

A regulator, non-coding technology, applied in DNA/RNA fragments, medical preparations containing active ingredients, drug combinations, etc., can solve the problems of affecting cell aging, complex relationship, abnormal expression and alternative splicing regulation and other problems

Pending Publication Date: 2021-07-23
SENISCA LTD
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  • Claims
  • Application Information

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Problems solved by technology

However, the relationship between these pathways is not straightforward; there is crosstalk between them and there are also dose, cell type, and environmental effects (Rhim et al., 2016)
Thus, activation of ERK and AKT signaling by classical aging stimuli such as DNA damage, inflammation, or growth factors may induce dysregulation of splicing factor expression and alternative splicing and affect cellular senescence

Method used

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  • Compositions comprising intermediate non-coding RNA regulators modulating the expression of etv6 or foxo1 and uses thereof
  • Compositions comprising intermediate non-coding RNA regulators modulating the expression of etv6 or foxo1 and uses thereof
  • Compositions comprising intermediate non-coding RNA regulators modulating the expression of etv6 or foxo1 and uses thereof

Examples

Experimental program
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Embodiment

[0084] The purpose of the experiments in this example is to study the effects of manipulating the ERK and AKT signaling pathways through chemical inhibition or targeted gene knockdown on the expression of splicing factors, cell senescence and proliferation kinetics in late-passage primary human fibroblasts.

[0085] 1. Increased phosphorylation of target proteins in the MEK / ERK and PI3K / AKT pathways in senescent cells

[0086] Cell cultures were considered senescent when the population doubling time slowed to figure 1 ). It was found that late passage human primary dermal fibroblasts reached senescence at PD=63. The earlier passage cells were at PD=25. We noted increased phosphorylation of AKT, CREB, ERK, GSK3α, MEK, and MSK2 signaling proteins in late-passage fibroblasts, whereas phosphorylation of GSK3β, HPS27, JNK, MKK3, MKK6, mTOR, p38, p58, p70SK6, or RSK1 proteins Phosphorylation was not significantly increased in these cells ( figure 2 A). Several of these targets ...

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Abstract

The present invention relates to: compositions for modulating the expression of FOXO1 and / or ETV6, the composition comprising one or more intermediate non-coding RNA regulators; attenuating splicing factor expression, the composition comprising an expression modulator of FOXO1 and / or ETV6; attenuating cell senescence and / or re-entry to cell cycle, the composition comprising an expression modulator of FOXO1 and / or ETV6 or their downstream targets related to splicing factor expression; or a composition capable of modulating splicing factor expression, the composition comprising one or more compounds able to bind to, or inhibit, FOXO1 and / or ETV6 genes or their downstream targets related to splicing factor expression. Such compositions have therapeutic benefits in the prevention, management, amelioration or treatment of an age-related disease or condition or cancer or also as a research tool / reagent.

Description

technical field [0001] The present invention relates to compositions for modulating the expression of FOXO1 and / or ETV6 or their targets involved in the regulation of splicing factors. Such compositions have therapeutic potential in the prevention, management, amelioration or treatment of aging-related diseases or disorders or cancer, and also have potential as research tools / reagents. Background technique [0002] Senescent cells are viable and metabolically active entities that have lost their ability to proliferate after multiple rounds of cell division and have been shown to accumulate in multiple tissues and in multiple species during aging (Faragher et al., 2017 ). Senescent cells release a cocktail of pro-inflammatory cytokines and remodeling proteins, termed the senescence-associated secretory phenotype (SASP), which paracrinely triggers senescence in neighboring cells and further stimulates inflammation in surrounding tissues (Salama et al., 2014). Accumulating e...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/47A61K48/00C12N15/113
CPCC12N15/113C12N15/1135C12N2310/113C12N2310/141C12N2310/11C12N2310/3233C12N2310/14A61K31/7105A61P43/00A61P35/00A61P39/00C12N2320/31
Inventor 洛娜·哈里斯伊娃·拉托尔
Owner SENISCA LTD
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