Aberrant non-canonical NF-κB signalling reprograms the epigenome landscape to drive oncogenic transcriptomes in multiple myeloma

In multiple myeloma, abnormal plasma cells establish oncogenic niches within the bone marrow by engaging the NF-κB pathway to nurture their survival while they accumulate pro-proliferative mutations. Under these conditions, many cases eventually develop genetic abnormalities endowing them with constitutive NF-κB activation. Here, we find that sustained NF-κB/p52 levels resulting from such mutations favours the recruitment of enhancers beyond the normal B-cell repertoire. Furthermore, through targeted disruption of p52, we characterise how such enhancers are complicit in the formation of super-enhancers and the establishment of cis-regulatory interactions with myeloma dependencies during constitutive activation of p52. Finally, we functionally validate the pathological impact of these cis-regulatory modules on cell and tumour phenotypes using in vitro and in vivo models, confirming RGS1 as a p52-dependent myeloma driver. We conclude that the divergent epigenomic reprogramming enforced by aberrant non-canonical NF-κB signalling potentiates transcriptional programs beneficial for multiple myeloma progression

Transcriptional regulation during aberrant activation of NF-κB signalling in cancer

The NF-κB signalling pathway is a major signalling cascade involved in the regulation of inflammation and innate immunity. It is also increasingly recognised as a crucial player in many steps of cancer initiation and progression. The five members of the NF-κB family of transcription factors are activated through two major signalling pathways, the canonical and non-canonical pathways. The canonical NF-κB pathway is prevalently activated in various human malignancies as well as inflammation-related disease conditions. Meanwhile, the significance of non-canonical NF-κB pathway in disease pathogenesis is also increasingly recognized in recent studies. In this review, we discuss the double-edged role of the NF-κB pathway in inflammation and cancer, which depends on the severity and extent of the inflammatory response. We also discuss the intrinsic factors, including selected driver mutations, and extrinsic factors, such as tumour microenvironment and epigenetic modifiers, driving aberrant activation of NF-κB in multiple cancer types. We further provide insights into the importance of the interaction of NF-κB pathway components with various macromolecules to its role in transcriptional regulation in cancer. Finally, we provide a perspective on the potential role of aberrant NF-κB activation in altering the chromatin landscape to support oncogenic development.National Research Foundation (NRF)Published versionThis work is funded by the National Research Foundation (NRF) Singapore, under its Singapore NRF Fellowship (NRF-NRFF2018-04)

Protein arginylation regulates cellular stress response by stabilizing HSP70 and HSP40 transcripts

Svrha rada bila je otkriti što turiste privlači u Hrvatsku, saznati koji faktori utječu na njihov dolazak, zašto se isti turisti vraćaju, te što je moguće učiniti kako bi oni bili još zadovoljniji. U istraživanju su korištene su: deskriptivna metoda, metode analize i sinteze, metoda indukcije i dedukcije te komparacije. U okviru anketnog upitnika ispitane su osnovne kategorije kao što su zadovoljstvo gastronomijom, ljepote kulturnih znamenitosti, čistoća plaža te ostalo. Na zadovoljstvo turista Hrvatskom kao turističkom destinacijom utječu i motivi njihova dolaska koji se znatno razlikuju. Povoljne cijene i pristupačnost domaćina u budućnosti neće biti dovoljna stavka za dolazak novih turista. Stoga je nužno poboljšati ponudu, sniziti cijene te turistima pružiti pravi omjer cijene i kvalitete. Iz dobivenih rezultata anketnog upitnika, moguće je zaključiti da je u svakoj ponuđenoj kategoriji u turizmu potrebno daljnje unapređenje, pri čemu je to u nekim područjima izraženije.Možemo zaključiti da je percepcija turista o Hrvatskoj kao turističkoj destinaciji kategorija koja itekako ostavlja mjesta za napredak

Efficient protocol for isolation of high-quality RNA from tea without using liquid nitrogen for molecular analysis

81-84<span style="font-size:9.0pt;font-family: " times="" new="" roman";mso-fareast-font-family:"times="" roman";mso-bidi-font-family:="" mangal;mso-ansi-language:en-gb;mso-fareast-language:en-us;mso-bidi-language:="" hi"="" lang="EN-GB">A good quality RNA is an important prerequisite for any downstream molecular analysis. However, isolation of quality RNA from tea is difficult due to presence of high amount of phenols and polysaccharides. We describe here an efficient protocol for total RNA isolation without liquid nitrogen from apical buds and tender leaves of tea. This protocol yielded RNA 1248±23 µg/g of fresh leaf tissue with high purity. The RNA was also found to be suitable for mRNA purification, cDNA synthesis and cloning through RT-PCR (reverse transcription-polymerase chain reaction) and cDNA library construction.</span