ABSTRACT
Iron (Fe) toxicity is a major issue adversely affecting rice production worldwide. Unfortunately, the physiological and genetic mechanisms underlying Fe toxicity tolerance in rice remain relatively unknown. In this study, we conducted a genome-wide association study using a diverse panel consisting of 551 rice accessions to identify genetic mechanisms and candidate genes associated with Fe toxicity tolerance. Of the 29 quantitative trait loci (QTL) for Fe toxicity tolerance detected on chromosomes 1, 2, 5, and 12, five (qSH_Fe5, qSFW_Fe2.3, qRRL5.1, qRSFW1.1, and qRSFW12) were selected to identify candidate genes according to haplotype and bioinformatics analyses. The following five genes were revealed as promising candidates: LOC_Os05g40160, LOC_Os05g40180, LOC_Os12g36890, LOC_Os12g36900, and LOC_Os12g36940. The physiological characteristics of rice accessions with contrasting Fe toxicity tolerance reflected the importance of reactive oxygen species-scavenging antioxidant enzymes and Fe homeostasis for mitigating the negative effects of Fe toxicity on rice. Our findings have clarified the genetic and physiological mechanisms underlying Fe toxicity tolerance in rice. Furthermore, we identified valuable genetic resources for future functional analyses and the development of Fe toxicity-tolerant rice varieties via marker-assisted selection.
Subject(s)
Haplotypes , Iron , Oryza , Quantitative Trait Loci , Oryza/genetics , Oryza/drug effects , Iron/metabolism , Iron/toxicity , Genome-Wide Association Study , Gene Expression Regulation, Plant/drug effects , Plant Proteins/genetics , Plant Proteins/metabolism , Genes, Plant , Polymorphism, Single NucleotideABSTRACT
Hepatocellular carcinoma (HCC) is the most common primary liver cancer worldwide and no pharmacological treatment is available that can achieve complete remission of HCC. Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is a recently identified HCC tumor suppressor gene which plays an important role in the development of HCC and its inactivation and reactivation has been shown to result in respectively HCC tumorigenesis and suppression. Small activating RNAs (saRNAs) have been used to achieve targeted activation of therapeutic genes for the restoration of their encoded protein through the RNAa mechanism. Here we designed and validated saRNAs that could activate LHPP expression at both the mRNA and protein levels in HCC cells. Activation of LHPP by its saRNAs led to the suppression of HCC proliferation, migration and the inhibition of Akt phosphorylation. When combined with targeted anticancer drugs (e.g., regorafenib), LHPP saRNA exhibited synergistic effect in inhibiting in vitro HCC proliferation and in vivo antitumor growth in a xenograft HCC model. Findings from this study provides further evidence for a tumor suppressor role of LHPP and potential therapeutic value of restoring the expression of LHPP by saRNA for the treatment of HCC.
Subject(s)
Carcinoma, Hepatocellular , Cell Proliferation , Inorganic Pyrophosphatase , Liver Neoplasms , Humans , Inorganic Pyrophosphatase/metabolism , Inorganic Pyrophosphatase/genetics , Cell Proliferation/drug effects , Animals , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/genetics , Liver Neoplasms/drug therapy , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/genetics , Mice , Cell Line, Tumor , Up-Regulation/drug effects , Xenograft Model Antitumor Assays , Cell Movement/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Mice, NudeABSTRACT
Introduction: Rice (Oryza sativa L.) production is being challenged by global warming. Identifying new loci and favorable alleles associated with heat tolerance is crucial to developing rice heat-tolerant varieties. Methods: We evaluated the heat tolerance at the seedling stage using 620 diverse rice accessions. A total of six loci associated with heat tolerance were identified by a genome-wide association study (GWAS) with ~2.8 million single nucleotide polymorphisms (SNPs). Results: Among the six detected loci, qHT7 harbored the strongest association signal and the most associated SNPs. By comparing the transcriptomes of two representative accessions with contrasting heat tolerance, LOC_Os07g48710 (OsVQ30) was selected as a promising candidate gene in qHT7 due to the significant difference in its expression level between the two accessions. Haplotype 4 (Hap4) of LOC_Os07g48710 was determined as the favorable haplotype for heat tolerance via the gene-based haplotype analysis. The heat-tolerant haplotype LOC_Os07g48710Hap4 is highly enriched in the tropical Geng/Japonica accessions, and its frequency has decreased significantly during the improvement process of rice varieties. Discussion: Based on the GWAS and transcriptomics integrated results, a hypothetical model modulated by qHT7 in response to heat stress was proposed. Our results provide valuable candidate genes for improving rice heat tolerance through molecular breeding.