[Long non-coding RNAs, new therapeutic targets for the treatment of non-small cell lung cancers?].

A better understanding of the molecular mechanisms associated with the aggressiveness and high recurrence rate of non-small cell lung cancers is needed to identify new biomarkers and therapeutic targets to improve patient management. In this context, this review provides a non-exhaustive update on the emerging family of long non-coding RNAs, important regulators of gene expression, frequently deregulated in cancers and in response to hypoxia - an environmental factor that plays an important role in the development, aggressiveness and treatment resistance of these tumors.

Identification of miR-141 as a Regulator of Epidermal Homeostasis.

MicroRNAs, small endogenous noncoding RNAs, are involved in the regulation of epidermal homeostasis. Among them, miR-203 was the most described and expressed in human epidermis, promoting keratinocyte (KC) differentiation by repressing genes involved in proliferation. To identify other microRNAs involved in this process, the miRNomes of normal human KCs cultured in monolayer (2-dimensional) or in 3-dimensional reconstructed skin were compared.

Detecting subtle transcriptomic perturbations induced by lncRNAs knock-down in single-cell CRISPRi screening using a new sparse supervised autoencoder neural network.

Single-cell CRISPR-based transcriptome screens are potent genetic tools for concomitantly assessing the expression profiles of cells targeted by a set of guides RNA (gRNA), and inferring target gene functions from the observed perturbations. However, due to various limitations, this approach lacks sensitivity in detecting weak perturbations and is essentially reliable when studying master regulators such as transcription factors. To overcome the challenge of detecting subtle gRNA induced transcriptomic perturbations and classifying the most responsive cells, we developed a new supervised autoencoder neural network method.

Identification and functional validation of SRC and RAPGEF1 as new direct targets of miR-203, involved in regulation of epidermal homeostasis.

The epidermis is mostly composed of keratinocytes and forms a protecting barrier against external aggressions and dehydration. Epidermal homeostasis is maintained by a fine-tuned balance between keratinocyte proliferation and differentiation. In the regulation of this process, the keratinocyte-specific miR-203 microRNA is of the outmost importance as it promotes differentiation, notably by directly targeting and down-regulating mRNA expression of genes involved in keratinocyte proliferation, such as ΔNp63, Skp2 and Msi2.

KRAS and NRAS Translation Is Increased upon MEK Inhibitors-Induced Processing Bodies Dissolution.

Overactivation of the mitogen-activated protein kinase (MAPK) pathway is a critical driver of many human cancers. However, therapies directly targeting this pathway lead to cancer drug resistance. Resistance has been linked to compensatory RAS overexpression, but the mechanisms underlying this response remain unclear.