Candidate genes conferring ethylene-response in cultivated peanuts determined by BSA-seq and fine-mapping

Ethylene plays essential roles in plant growth,development and stress responses.The ethylene signaling pathway and molecular mechanism have been studied extensively in Arabidopsis and rice but limited in peanuts.Here,we established a sand-culture method to screen pingyangmycin mutagenized peanut lines based on their specific response to ethylene(“triple response”).An ethylene-insensitive mutant,inhibition of peanut hypocotyl elongation 1(iph1),was identified that showed reduced sensitivity to ethylene in both hypocotyl elongation and root growth.Through bulked segregant analysis sequencing,a major gene related to iph1,named AhIPH1,was preliminarily mapped at the chromosome Arahy.01,and further narrowed to a 450-kb genomic region through substitution mapping strategy.A total of 7014 genes were differentially expressed among the ACC treatment through RNA-seq analysis,of which only the Arahy.5BLU0Q gene in the candidate mapping interval was differentially expressed between WT and mutant iph1.Integrating sequence variations,functional annotation and transcriptome analysis revealed that a predicated gene,Arahy.5BLU0Q,encoding SNF1 protein kinase,may be the candidate gene for AhIPH1.This gene contained two single-nucleotide polymorphisms at promoter region and was more highly expressed in iph1 than WT.Our findings reveal a novel ethylene-responsive gene,which provides a theoretical foundation and new genetic resources for the mechanism of ethylene signaling in peanuts.

Cellular metabolism: A key player in cancer ferroptosis

Cellular metabolism is the fundamental process by which cells maintain growth and self-renewal.It produces energy,furnishes raw materials,and intermedi-ates for biomolecule synthesis,and modulates enzyme activity to sustain normal cellular functions.Cellular metabolism is the foundation of cellular life processes and plays a regulatory role in various biological functions,including pro-grammed cell death.Ferroptosis is a recently discovered form of iron-dependent programmed cell death.The inhibition of ferroptosis plays a crucial role in tumorigenesis and tumor progression.However,the role of cellular metabolism,particularly glucose and amino acid metabolism,in cancer ferroptosis is not well understood.Here,we reviewed glucose,lipid,amino acid,iron and sele-nium metabolism involvement in cancer cell ferroptosis to elucidate the impact of different metabolic pathways on this process.Additionally,we provided a detailed overview of agents used to induce cancer ferroptosis.We explained that the metabolism of tumor cells plays a crucial role in maintaining intracellu-lar redox homeostasis and that disrupting the normal metabolic processes in these cells renders them more susceptible to iron-induced cell death,resulting in enhanced tumor cell killing.The combination of ferroptosis inducers and cel-lular metabolism inhibitors may be a novel approach to future cancer therapy and an important strategy to advance the development of treatments.

Altered glycosylation in cancer: molecular functions and therapeutic potential

Glycosylation,a key mode of protein modification in living organisms,is critical in regulating various biological functions by influencing protein folding,transportation,and localization.Changes in glycosylation patterns are a significant feature of cancer,are associated with a range of pathological activities in cancer-related processes,and serve as critical biomarkers providing new targets for cancer diagnosis and treatment.Glycoproteins like human epidermal growth factor receptor 2(HER2)for breast cancer,alpha-fetoprotein(AFP)for liver cancer,carcinoembryonic antigen(CEA)for colon cancer,and prostatespecific antigen(PSA)for prostate cancer are all tumor biomarkers approved for clinical use.Here,we introduce the diversity of glycosylation structures and newly discovered glycosylation substrate—glycosylated RNA(glycoRNA).This article focuses primarily on tumor metastasis,immune evasion,metabolic reprogramming,aberrant ferroptosis responses,and cellular senescence to illustrate the role of glycosylation in cancer.Additionally,we summarize the clinical applications of protein glycosylation in cancer diagnostics,treatment,and multidrug resistance.We envision a promising future for the clinical applications of protein glycosylation.

AFAP1-AS1: a rising star among oncogenic long non-coding RNAs

Long non-coding RNAs(lncRNAs)have become a hotspot in biomedical research.This interest reflects their extensive involvement in the regulation of the expression of other genes,and their influence on the occurrence and development of a variety of human diseases.Actin filament associated protein 1-Antisense RNA 1(AFAP1-AS1)is a recently discovered oncogenic lncRNA.It is highly expressed in a variety of solid tumors,and regulates the expression of downstream genes and signaling pathways through adsorption and competing microRNAs,or by the direct binding to other proteins.Ultimately,AFAP1-AS1 promotes proliferation,chemotherapy resistance,and resistance to apoptosis,maintains stemness,and enhances invasion and migration of tumor cells.This paper summarizes the research concerning AFAP1-AS1 in malignant tumors,including the clinical application prospects of AFAP1-AS1 as a potential molecular marker and therapeutic target of malignant tumors.We also discuss the limitations in the knowledge of AFAP1-AS1 and directions of further research.AFAP1-AS1 is expected to provide an example for studies of other lncRNA molecules.

Long non-coding RNA AFAP1-AS1 accelerates lung cancer cells migration and invasion by interacting with SNIP1 to upregulate c-Myc

Actin filament associated protein 1 antisense RNA 1(named AFAP1-AS1)is a long non-coding RNA and overexpressed in many cancers.This study aimed to identify the role and mechanism of AFAP1-AS1 in lung cancer.The AFAP1-AS1 expression was firstly assessed in 187 paraffin-embedded lung cancer and 36 normal lung epithelial tissues by in situ hybridization.The migration and invasion abilities of AFAP1-AS1 were investigated in lung cancer cells.To uncover the molecular mechanism about AFAP1-AS1 function in lung cancer,we screened proteins that interact with AFAP1-AS1 by RNA pull down and the mass spectrometry analyses.AFAP1-AS1 was highly expressed in lung cancer clinical tissues and its expression was positively correlated with lung cancer patients'poor prognosis.In vivo experiments confirmed that AFAP1-AS1 could promote lung cancer metastasis.AFAP1-AS1 promoted lung cancer cells migration and invasion through interacting with Smad nuclear interacting protein 1(named SNIP1),which inhibited ubiquitination and degradation of c-Myc protein.Upregulation of c-Myc molecule in turn promoted the expression of ZEB1,ZEB2,and SNAIL gene,which ultimately enhanced epithelial to mesenchymal transition(EMT)and lung cancer metastasis.Understanding the molecular mechanism by which AFAP1-AS1 promotes lung cancer's migration and invasion may provide novel therapeutic targets for lung cancer patients'early diagnosis and therapy.