The outpost against cancer:universal cancer only markers

Cancer is the leading cause of death worldwide.Early detection of cancer can lower the mortality of all types of cancer;however,effective early-detection biomarkers are lacking for most types of cancers.DNA methylation has always been a major target of interest because DNA methylation usually occurs before other detectable genetic changes.While investigating the common features of cancer using a novel guide positioning sequencing for DNA methylation,a series of universal cancer only markers(UCOMs)have emerged as strong candidates for effective and accurate early detection of cancer.While the clinical value of current cancer biomarkers is diminished by low sensitivity and/or low specificity,the unique characteristics of UCOMs ensure clinically meaningful results.Validation of the clinical potential of UCOMs in lung,cervical,endometrial,and urothelial cancers further supports the application of UCOMs in multiple cancer types and various clinical scenarios.In fact,the applications of UCOMs are currently under active investigation with further evaluation in the early detection of cancer,auxiliary diagnosis,treatment efficacy,and recurrence monitoring.The molecular mechanisms by which UCOMs detect cancers are the next important topics to be investigated.The application of UCOMs in real-world scenarios also requires implementation and refinement.

Hymecromone:a clinical prescription hyaluronan inhibitor for efficiently blocking COVID-19 progression

Currently,there is no effective drugs for treating clinically COVID-19 except dexamethasone.We previously revealed that human identical sequences of SARS-CoV-2 promote the COVID-19 progression by upregulating hyaluronic acid(HA).As the inhibitor of HA synthesis,hymecromone is an approved prescription drug used for treating biliary spasm.Here,we aimed to investigate the relation between HA and COVID-19,and evaluate the therapeutic effects of hymecromone on COVID-19.Firstly,HA was closely relevant to clinical parameters,including lymphocytes(n=158;r=−0.50;P<0.0001),C-reactive protein(n=156;r=0.55;P<0.0001),D-dimer(n=154;r=0.38;P<0.0001),and fibrinogen(n=152;r=0.37;P<0.0001),as well as the mass(n=78;r=0.43;P<0.0001)and volume(n=78;r=0.41;P=0.0002)of ground-glass opacity,the mass(n=78;r=0.48;P<0.0001)and volume(n=78;r=0.47;P<0.0001)of consolidation in patient with low level of hyaluronan(HA<48.43 ng/mL).Furthermore,hyaluronan could directly cause mouse pulmonary lesions.Besides,hymecromone remarkably reduced HA via downregulating HAS2/HAS3 expression.Moreover,89%patients with hymecromone treatment had pulmonary lesion absorption while only 42%patients in control group had pulmonary lesion absorption(P<0.0001).In addition,lymphocytes recovered more quickly in hymecromone-treated patients(n=8)than control group(n=5)(P<0.05).These findings suggest that hymecromone is a promising drug for COVID-19 and deserves our further efforts to determine its effect in a larger cohort.

Mutually exclusive epigenetic modification on SIX6 with hypermethylation for precancerous stage and metastasis emergence tracing

Dear Editor,Aberrant DNA methylation gets involved in cancer initiation,progression,and recurrence,which in turn makes it an ideal cancer biomarker.Various methylation markers or their panels have been developed in diverse cancer types.However,the model-constructing based marker mining strategy and incompatibility of application have greatly impeded their ways to clinic.Thus,single methylation marker applicable to all/most cancer types and multiple clinical scenarios is desperately needed.The hope came from the unexpected observation that HIST1H4F was universally hypermethylated in all 17 cancer types;thus,we raised the concept of“Universal Cancer Only Marker(UCOM)”and established a paradigm for discovery and clinical application of UCOM.1 Recently,a novel UCOM,hypermethylated PCDHGB7,was identified and found to advance cervical cancer(CC)screening to the precancerous stage.2 During the screening of UCOM,we discerned a bunch of cancer cell-differentially methylated regions.1 Among them,sine oculis(SIX)homeobox family of transcription factors,which were found to function as tumorigenesis regulator by promoting epithelial-to-mesenchymal transition and metastasis recently in addition to their traditional roles in tissue formation and organogenesis,3 sparked our special attention.Herein,we interrogate whether SIX6 methylation could serve as a novel UCOM and its potential applications.

Steering Against Wind： A New Network of NamiRNAs and Enhancers

Micro RNAs(miRNAs) are a class of endogenous non-coding RNAs with regulatory functions. Traditionally, miRNAs are thought to play a negative regulatory role in the cytoplasm by binding to the 30 UTR of target genes to degrade m RNA or inhibit translation. However, it remains a challenge to interpret the potential function of many miRNAs located in the nucleus.Recently, we reported a new type of miRNAs present in the nucleus, which can activate gene expression by binding to the enhancer, and named them nuclear activating miRNAs(NamiRNAs). The discovery of NamiRNAs showcases a complementary regulatory mechanism of mi RNA, demonstrating their differential roles in the nucleus and cytoplasm. Here, we reviewed miRNAs in nucleus to better understand the function of NamiRNAs in their interactions with the enhancers. Accordingly, we propose a Nami RNA–enhancer–target gene activation network model to better understand the crosstalk between NamiRNAs and enhancers in regulating gene transcription.Moreover, we hypothesize that NamiRNAs may be involved in cell identity or cell fate determination during development, although further study is needed to elucidate the underlying mechanisms in detail.

Viral miRNA-mediated activation of hyaluronan production as a drug target against COVID-19

The global coronavirus disease 2019(COVID-19)pandemic has caused more than 6.1 million deaths until March 24,2022,as reported by the World Health Organization(WHO).Recently,breakthrough infections have appeared in individuals fully vaccinated against SARS-Co V-2^(1),which could be attributed to the rapid mutation of the RNA virus2.Currently,following the Delta variant,the Omicron variant of SARS-Co V-2 is increasingly becoming the dominant epidemic strain in the world.