Acta biochimica et biophysica Sinica最新文献

Small RNA (sRNA)-mediated RNA interference (RNAi) is a sequence-specific gene silencing mechanism that modulates gene expression in eukaryotes. As core molecules of RNAi, various sRNAs are encoded in the plant genome or derived from invading RNA molecules, and their biogenesis depends on distinct genetic pathways. Transitive small interfering RNAs (siRNAs), which are sRNAs produced from double-strand RNA (dsRNA) in a process that depends on RNA-dependent RNA polymerases (RDRs), can amplify and spread silencing signals to additional transcripts, thereby enabling a phenomenon termed "transitive RNAi". Members of this class of siRNAs function in various biological processes ranging from development to stress adaptation. In Arabidopsis thaliana, two RDRs participate in the generation of transitive siRNAs, acting cooperatively with various siRNA generation-related factors, such as the RNA-induced silencing complex (RISC) and aberrant RNAs. Transitive siRNAs are produced in diverse subcellular locations and structures under the control of various mechanisms, highlighting the intricacies of their biogenesis and functions. In this review, we discuss recent advances in understanding the molecular events of transitive siRNA biogenesis and its regulation, with a particular focus on factors involved in RDR recruitment. We aim to provide a comprehensive description of the generalized mechanism governing the biogenesis of transitive siRNAs. Additionally, we present an overview of the diverse biological functions of these siRNAs and raise some pressing questions in this area for further investigation.

Esophageal cancer (EC) is one of the most recalcitrant cancers, with a 5-year survival rate of <30%. The hydroxyacyl-CoA dehydrogenase alpha subunit (HADHA) plays an essential role in long-chain fatty acid metabolism, and dysregulation of HADHA has been demonstrated to be involved in a series of metabolic diseases and cancers. However, its role in cancers remains controversial. HADHA has seldom been investigated in EC, and little is known about how HADHA regulates the malignant progression of EC. In this study, we find that HADHA is significantly upregulated in EC tissues and is correlated with poor survival. HADHA knockdown markedly inhibits EC cell proliferation both in vitro and in vivo. The loss of HADHA also induces EC cell apoptosis, causes cell cycle arrest and inhibits cell migration. Additionally, RNA profiling reveals that mTOR signaling is significantly suppressed after HADHA knockdown. Mechanistically, HADHA interacts with SP1 and induces MDM2 expression. In conclusion, both mTOR signaling and the SP1-MDM2 axis participate in the HADHA-induced malignant behavior of EC cells.

Biological development and genetic information transfer are governed by genetic, epigenetic, transcriptional, and posttranscriptional mechanisms. RNA methylation, the attachment of methyl (-CH ₃) groups to RNA molecules, is a posttranscriptional modification that has gained increasing attention in recent years because of its role in RNA epitranscriptomics. RNA modifications (RMs) influence various aspects of RNA metabolism and are involved in the regulation of diverse biological processes and diseases. Neural cell types emerge at specific stages of brain development, and recent studies have revealed that neurodevelopment, aging, and disease are tightly linked to transcriptome dysregulation. In this review, we discuss the roles of N6-methyladenine (m6A) and 5-methylcytidine (m5C) RNA modifications in neurodevelopment, physiological functions, and related diseases.

Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) is involved in tumorigenicity through DNA methylation in various cancers, including breast cancer. This study aims to investigate the regulatory mechanisms of UHRF1 in breast cancer progression. Herein, we show that UHRF1 is upregulated in breast cancer tissues and cell lines as measured by western blot analysis and immunohistochemistry. Breast cancer cells are transfected with a UHRF1 overexpression plasmid (pcDNA-UHRF1) or short hairpin RNA targeting UHRF1 (sh-UHRF1), followed by detection of cell proliferation, invasion, apoptosis, and cell cycle. UHRF1 overexpression promotes proliferation and invasion and attenuates cell cycle arrest and apoptosis in breast cancer cells, while UHRF1 knockdown shows the opposite effect. Moreover, methylation-specific PCR and ChIP assays indicate that UHRF1 inhibits zinc finger and BTB domain containing 16 (ZBTB16) expression by promoting ZBTB16 promoter methylation via the recruitment of DNA methyltransferase 1 (DNMT1). Then, a co-IP assay is used to verify the interaction between ZBTB16 and the annexin A7 (ANXA7) protein. ZBTB16 promotes ANXA7 expression and subsequently inhibits Cyclin B1 expression. Rescue experiments reveal that ZBTB16 knockdown reverses the inhibitory effects of UHRF1 knockdown on breast cancer cell malignancies and that ANXA7 knockdown abolishes the inhibitory effects of ZBTB16 overexpression on breast cancer cell malignancies. Additionally, UHRF1 knockdown significantly inhibits xenograft tumor growth in vivo. In conclusion, UHRF1 knockdown inhibits proliferation and invasion, induces cell cycle arrest and apoptosis in breast cancer cells via the ZBTB16/ANXA7/Cyclin B1 axis, and reduces xenograft tumor growth in vivo.

Hepatocellular carcinoma (HCC), the predominant type of liver cancer, is an aggressive malignancy with limited therapeutic options. In this study, we assess a collection of newly designed gold(I) phosphine complexes. Remarkably, the compound GC002 exhibits the greatest toxicity to HCC cells and outperforms established medications, such as sorafenib and auranofin, in terms of antitumor efficacy. GC002 triggers irreversible necroptosis in HCC cells by increasing the intracellular accumulation of reactive oxygen species (ROS). Mechanistically, GC002 significantly suppresses the activity of thioredoxin reductase (TrxR), which plays a crucial role in regulating redox homeostasis and is often overexpressed in HCC by binding directly to the enzyme. Our in vivo xenograft study confirms that GC002 possesses remarkable antitumor activity against HCC without severe side effects. These findings not only highlight the novel mechanism of controlling necroptosis via TrxR and ROS but also identify GC002 as a promising candidate for the further development of antitumor agents targeting HCC.