Upstream regulators and downstream effectors of NF-κB in Alzheimer's disease.

Since Alzheimer's disease (AD) is becoming the prevalent dementia in the whole world, more underlying mechanisms are emerging. Long time has the transcription factor NF-κB been identified to participate in AD pathogenesis, various studies have focused on the causes and effects of AD that are linked to NF-κB. In this review we discuss diverse environmental stimuli including oxidative stress, neuroinflammation and metabolism, involved signaling pathways such as PI3K/AKT, MAPK and AGE/RAGE/GSK-3 and newly found ncRNAs that mediate neuron toxicity or neuron protection through NF-κB activation and the following response associated with the same factors in AD. These may provide future orientation of investigation at transcription level and support efficient treatment to AD by a better understanding of the upstream regulators and downstream effectors of NF-κB.

Hypoxia-regulated lncRNAs in cancer.

Hypoxic regions are common in solid tumors and have an impact on tumor progression and on the therapeutic response. However, the underlying mechanism for hypoxic tumor microenvironment has not been entirely elucidated. Recently, long noncoding RNAs (lncRNAs) are being increasingly recognized to contribute to carcinogenesis through diverse mechanisms. To date, several lncRNAs have been described in hypoxia-associated cancer process, implying a potential role in maintaining cellular homeostasis and enabling an adaptive survival under hypoxic stress conditions. While it has been widely accepted that a complex cellular network of gene products, such as protein and miRNA, take part in hypoxic cancer progression, it remains largely elusive how lncRNAs participate in it. In this review, we introduce an update view of lncRNAs, focusing on hypoxia-related lncRNAs. We hereby summarize the cause and consequence of hypoxia-modulated lncRNAs in cancer as well as their functional mechanisms, highlighting the specific roles of lncRNAs in hypoxia response in cancer.

YAP and TAZ Take Center Stage in Cancer.

The Hippo pathway was originally identified and named through screening for mutations in Drosophila, and the core components of the Hippo pathway are highly conserved in mammals. In the Hippo pathway, MST1/2 and LATS1/2 regulate downstream transcription coactivators YAP and TAZ, which mainly interact with TEAD family transcription factors to promote tissue proliferation, self-renewal of normal and cancer stem cells, migration, and carcinogenesis. The Hippo pathway was initially thought to be quite straightforward; however, recent studies have revealed that YAP/TAZ is an integral part and a nexus of a network composed of multiple signaling pathways. Therefore, in this review, we will summarize the latest findings on events upstream and downstream of YAP/TAZ and the ways of regulation of YAP/TAZ. In addition, we also focus on the crosstalk between the Hippo pathway and other tumor-related pathways and discuss their potential as therapeutic targets.

The ways of action of long non-coding RNAs in cytoplasm and nucleus.

Over the past fifteen years, small regulatory RNAs, such as siRNA and miRNA, have been extensively investigated and the underlying molecular mechanisms have been well documented, suggesting that ncRNAs play a major function in many cellular processes. An expanding body of evidence reveals that long non-coding RNAs (lncRNAs), once described as dark matter, are involved in diverse cellular progresses, including regulation of gene expression, dosage compensation, genomic imprinting, nuclear organization and nuclear-cytoplasm trafficking via a number of complex mechanisms. The emerging links between lncRNAs and diseases as well as their tissue-specific expression patterns also indicate that lncRNAs comprise a core transcriptional regulatory circuitry. The function of lncRNAs is based on their sequence and structure; and they can combine with DNA, RNA, and proteins both in the nucleus and the cytoplasm. However, detailed insights into their biological and mechanistic functions are only beginning to emerge. In this review, we will mainly talk about diverse ways of action of lncRNAs in different sub-cellular locations and provide clues for following studies.