Editorial: Evolving roles of piRNAs in solid tumors

According to Global Cancer Statistics 2020, an estimated 19.3 million new cancer cases and almost 10 million cancer deaths occurred in 2020. Solid tumors represent approximately 90% of adult human cancers, hence they warrant significant attention from the research fraternity to improve upon the existing platforms of treatment and management of the malignancy. Only by a better understanding of the biology associated with cancer development and progression can we identify clinically relevant novel molecular targets that can not only improve upon the risk stratification of the patients, but also assist in overall disease management. PIWI-interacting RNA (piRNA) is a class of small non-coding RNA (26-31nt) that interacts with PIWI proteins to form the piRNA silencing complex (piRISC). PIWI is a subfamily of Argonaute, and piRNA must bind to PIWI to exert its regulatory role, although have been also described PIWI independent functions for piRNAs. Nearly 10 million unique piRNA sequences (2) have now been identified in humans alone that have been recognized to play a wide variety of roles including germline development, maintenance, and protection of the genome integrity by repressing the activity of transposons through post-transcriptional silencing or other epigenetic mechanisms. Emerging data suggests that piRNAs also have strong regulatory roles within the somatic tissues where they regulate gene expression by inducing histone modification and DNA methylation. Owing to their remarkable roles in maintaining cellular homeostasis, it is not surprising that the expression of piRNAs is reported to be frequently deregulated in several cancers. Current studies indicated that piRNAs are significantly abnormally expressed and are involved in the initiation, progression, and metastasis of different solid tumors, which may be the potential diagnostic tools, prognostic markers, and therapeutic targets for cancers. This special issue is a collection of original research and review articles on this topic

MIR135A1 (microRNA 135a-1)

Review on MIR135A1, with data on DNA/RNA and where the gene is implicated

The role of ncRNAs in solid tumors prognosis: from laboratory to clinical utility

Today we know that non-coding RNAs (ncRNAs) represent most of the transcribed human genome and participate in relevant cellular processes. NcRNAs regulate from RNA transcription to protein translation, have important epigenetic roles or facilitate protein–protein interactions among other functions. In consequence, their dysregulation has been associated with tumor development and progression. Recently, their expression has also been detected in body fluids, opening the use of circulating ncRNAs for diagnosis and for evaluation and monitoring cancer prognosis

Tratamiento de la gonartrosis con osteotomía tibial de penetración y fijación con grapas

La osteotomía metafisaria proximal de tibia ha sido utilizada en el tratamiento de 96 gonartrosis con desviación axil en varo (87 casos) o en valgo (nueve casos), con componente de flexo en la mitad de los casos y con cierto grado de laxitud ligamentosa en 1/3 de los casos. Se utilizó un cálculo angular preoperatorio en bipedestación con contraste opaco del eje mecánico de la extremidad y Rx-TV. La osteotomía fue cuneiforme de penetración, se estabilizó con grapas y se aplicó calza de yeso para facilitar el apoyo precoz. Proporcionó un efecto antiálgico en el 94 % de los casos, pero la valoración funcional deja el resultado en 25 % de casos excelentes y 51% de casos buenos. Destacan la necesidad de operar ambas rodillas, la bondad del resultado con independencia del grado de angulación, la compensación de las laxitudes moderadas ya referidas y la repercusión favorable del realineamiento axil sobre la artrosis femoropatelar presente en el 75 % de los casos

Gemcitabine Functions Epigenetically by Inhibiting Repair Mediated DNA Demethylation

Gemcitabine is a cytotoxic cytidine analog, which is widely used in anti-cancer therapy. One mechanism by which gemcitabine acts is by inhibiting nucleotide excision repair (NER). Recently NER was implicated in Gadd45 mediated DNA demethylation and epigenetic gene activation. Here we analyzed the effect of gemcitabine on DNA demethylation. We find that gemcitabine inhibits specifically Gadd45a mediated reporter gene activation and DNA demethylation, similar to the topoisomerase I inhibitor camptothecin, which also inhibits NER. In contrast, base excision repair inhibitors had no effect on DNA demethylation. In Xenopus oocytes, gemcitabine inhibits DNA repair synthesis accompanying demethylation of oct4. In mammalian cells, gemcitabine induces DNA hypermethylation and silencing of MLH1. The results indicate that gemcitabine induces epigenetic gene silencing by inhibiting repair mediated DNA demethylation. Thus, gemcitabine can function epigenetically and provides a tool to manipulate DNA methylation

DNA Damage Stress and Inhibition of Jak2-V617F Cause Its Degradation and Synergistically Induce Apoptosis through Activation of GSK3β

The cytoplasmic tyrosine kinase Jak2 plays a crucial role in cytokine receptor signaling in hematopoietic cells. The activated Jak2-V617F mutant is present in most cases of BCR/ABL-negative myeloproliferative neoplasms and constitutively activates downstream signals from homodimeric cytokine receptors, such as the erythropoietin receptor (EpoR). Here we examine the effects of DNA damage stress on Jak2 or Jak2-V617F and on induction of apoptosis in hematopoietic cells. Etoposide or doxorubicin dose-dependently decreased the expression level of Jak2 in UT7 or 32D cells expressing EpoR in the absence of Epo and that of exogenously expressed Jak2-V617F in UT7 cells when cotreated with the Jak2 inhibitor JakI-1 or AG490. Studies with pharmacological inhibitors and genetic manipulations further showed that downregulation of the PI3K/Akt pathway leading to the activation of GSK3β may be involved in downregulation of Jak2 or Jak2-V617F as well as in synergistic induction of Bax activation and apoptosis. The downregulation of Jak2 was inhibited by the proteasome inhibitor MG132 or by expression of both of loss-of-function mutants of c-Cbl and Cbl-b, E3 ubiquitin ligases which facilitated ubiquitination of Jak2-V617F when co-expressed in 293T cells. The pan-caspase inhibitor Boc-d-fmk also inhibited the Jak2 downregulation as well as appearance of a 100-kDa fragment that contained the N-terminal portion of Jak2 in response to DNA damage. Together, these data suggest that DNA damage stress with simultaneous inhibition of the kinase activity causes degradation of Jak2 or Jak2-V617F by caspase cleavage and proteasomal degradation through GSK3β activation, which is closely involved in synergistic induction of apoptosis in hematopoietic cells

Microbial ecology evaluation of an iberian pig processing plant through implementing sch sensors and the influence of the resident microbiota on Listeria monocytogenes

This study was supported by Research Project grants RTI2018-098267-R-C32 from the Spanish Ministerio de Ciencia, Innovaci?n y Universidades. Acknowledgments: The authors thank Dolors Busquets Soler for her technical assistance in the laboratory and Sarah Davies for the English grammar review.There is a whole community of microorganisms capable of surviving the cleaning and disinfection processes in the food industry. These persistent microorganisms can enhance or inhibit biofilm formation and the proliferation of foodborne pathogens. Cleaning and disinfection protocols will never reduce the contamination load to 0; however, it is crucial to know which resident species are present and the risk they represent to pathogens, such as Listeria monocytogenes, as they can be further used as a complementary control strategy. The aim of this study was to evaluate the resident surface microbiota in an Iberian pig processing plant after carrying out the cleaning and disinfection processes. To do so, surface sensors were implemented, sampled, and evaluated by culture plate count. Further, isolated microorganisms were identified through biochemical tests. The results show that the surfaces are dominated by Bacillus spp., Pseudomonas spp., different enterobacteria, Mannheimia haemolytica, Rhizobium radiobacter, Staphylococcus spp., Aeromonas spp., lactic acid bacteria, and yeasts and molds. Moreover, their probable relationship with the presence of L. monocytogenes in three areas of the plant is also explained. Further studies of the resident microbiota and their interaction with pathogens such as L. monocytogenes are required. New control strategies that promote the most advantageous profile of microorganisms in the resident microbiota could be a possible alternative for pathogen control in the food industry. To this end, the understanding of the resident microbiota on the surfaces of the food industry and its relation with pathogen presence is crucial