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Background: Sorafenib, an orally active potent tyrosine kinase inhibitor (TKI), represented a primary treatment in patients with advanced hepatocellular carcinoma (HCC). Unfortunately, sorafenib resistance was regarded as a huge obstacle for HCC treatment., Methods: RNA-sequencing including circRNA Sequencing (circRNA-Seq) for circular RNAs (circRNAs), miRNA Sequencing (miRNA-Seq) for microRNAs (miRNAs), as well as mRNA Sequencing (mRNA-Seq) for mRNAs in sorafenib-resistant HCC cells vs sorafenib-sensitive HCC cells , were performed. Then, interaction correlation analysis between differentially expressed circRNAs and miRNAs and their target genes in Huh7/SOR and SMMC7721/SOR cells was exhibited. The "circRNA-miRNA-mRNA" network was constructed through the Cytoscape software application, Circular RNA Interactome and Targetscan prediction, RNA binding protein immunoprecipitation (RIP), RNA pull-down, and Dual luciferase reporter assay . Furthermore, mRNA-Seq, Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for the downstream genes involved in the "circRNA-miRNA-mRNA" network was implemented. Iron detection assay, Lipid peroxidation quantification assay, ROS measurement assay, CCK-8 assay, and tumor challenge in vivo were used to determine the mechanisms promoting sorafenib resistance in HCC, where the "circRNA-miRNA-mRNA" network is clearly involved in., Results : circ_0001944 and circ_0078607 with upregulation and 2 downregulated expressed circRNAs (circ_0002874 and circ_0069981), as well as 11 upregulated miRNAs including miR-193a-5p, miR-197-3p, miR-27a-5p, miR-551b-5p, miR-335-3p, miR-767-3p, miR-767-5p, miR-92a-1-5p, miR-92a-3p, miR-3940-3p, and miR-664b-3p and 3 downregulated expressed miRNAs (miR-1292-5p, let-7c-5p, and miR-99a-5p) in sorafenib-resistant HCC cells were determined. Among these non-coding RNAs (ncRNAs), circ_0001944 and miR-1292-5p should not be drop out of sight; circ_0001944 has been proved to target miR-1292-5p to inhibit its expression in HCC. Subsequent findings also raise that miR-1292-5p directly targeted the 3'-noncoding region (3'-UTR) of Fibulin 2 (FBLN2) mRNA. Furthermore, circ_0001944 targets the miR-1292-5p/FBLN2 axis to inhibit cell ferroptosis in which the indicated regulators associated with iron overload and lipid peroxidation were "rearranged". Most importantly, circ_0001944 advanced sorafenib resistance in HCC through mitigating ferroptosis, where the miR-1292-5p/FBLN2 axis cannot be left unrecognized., Conclusion : Circ_0001944 is a putative target for reversing sorafenib resistance in HCC. Our findings are expected to provide new targets and new directions for sorafenib sensitization in the treatment of HCC., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Jing et al.)

[Display omitted] • miRNAs are important regulators of gene expression in plants. • Plant miRNAs play a pivotal role in abiotic stress responses. • Using high-throughput sequencing plant stress-responsive conserved and novel miRNAs can be identified. MicroRNAs (miRNAs) are a distinct groups of single-stranded non-coding, tiny regulatory RNAs approximately 20–24 nucleotides in length. miRNAs negatively influence gene expression at the post-transcriptional level and have evolved considerably in the development of abiotic stress tolerance in a number of model plants and economically important crop species. The present review aims to deliver the information on miRNA-mediated regulation of the expression of major genes or Transcription Factors (TFs), as well as genetic and regulatory pathways. Also, the information on adaptive mechanisms involved in plant abiotic stress responses, prediction, and validation of targets, computational tools, and databases available for plant miRNAs, specifically focus on their exploration for engineering abiotic stress tolerance in plants. The regulatory function of miRNAs in plant growth, development, and abiotic stresses consider in this review, which uses high-throughput sequencing (HTS) technologies to generate large-scale libraries of small RNAs (sRNAs) for conventional screening of known and novel abiotic stress-responsive miRNAs adds complexity to regulatory networks in plants. The discoveries of miRNA-mediated tolerance to multiple abiotic stresses, including salinity, drought, cold, heat stress, nutritional deficiency, UV-radiation, oxidative stress, hypoxia, and heavy metal toxicity, are highlighted and discussed in this review. [ABSTRACT FROM AUTHOR]

The intricate molecular network shared between diabetes mellitus (DM) and cancer has been broadly understood. DM has been associated with several hormone-dependent malignancies, including breast, pancreatic, and colorectal cancer (CRC). Insulin resistance, hyperglycemia, and inflammation are the main pathophysiological mechanisms linking DM to cancer. Non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are widely appreciated as pervasive regulators of gene expression, governing the evolution of metabolic disorders, including DM and cancer. The ways ncRNAs affect the development of DM complicated with cancer have only started to be revealed in recent years. Insulin-like growth factor 1 receptor (IGF-1R) signaling is a master regulator of pathophysiological processes directing DM and cancer. In this review, we briefly summarize a number of well-known miRNAs and lncRNAs that regulate the IGF-1R in DM and cancer, respectively, and further discuss the potential underlying molecular pathogenesis of this disease association. [ABSTRACT FROM AUTHOR]