Microplastics (MPs) have become a significant concern for their potential toxicity. However, the correlation between the size of plastic particles and their toxicity remains inconclusive. Here, we investigate the toxic effects of different sizes (80 nm, 800 nm, 8 µm and 80 µm) polystyrene MPs (PS-MPs) on the model organism Nile tilapia (Oreochromis niloticus). The results of bioluminescent imaging indicate that the 80 nm PS-MPs are more likely to invade the body. H&E staining shows severe damage on the intestinal villi and distinct hepatic steatosis in the 80 nm group. EdU labeling shows that the proliferation activity of intestinal and liver cells reduces significantly in the 80 nm group. The gut microbiome analysis shows a severe imbalance of gut microbiota homeostasis in the 80 nm group. The analysis of liver transcriptomics and metabolomics shows that the liver lipid metabolism is disordered in the 80 nm group. In conclusion, this study confirms that the 80 nm PS-MPs are more likely to induce intestinal and liver toxicity. All the above lay the foundation for further study on the pathological damage of MPs to other organisms.

Recent studies have suggested that ubiquitin-conjugating enzyme E2D1 (UBE2D1) is involved in tumor progression. In this study, we found that UBE2D1 expression was upregulated in breast cancer (BC) and was related to the prognosis of BC patients. Through in vitro and in vivo experiments, we demonstrated the aberrant expression of UBE2D1 promoted the proliferation and migration of BC cells, and the IGF2BP2-mediated N6-methyladenosine (m6A) modification increased the stability of UBE2D1 mRNA. Mechanistically, UBE2D1 expression regulated the activity of TGF-β signaling through modulating the expression and the phosphorylation level of Smad2/3. Furthermore, UBE2D1 directly bound to Smad2/3 and affected the subsequent binding of Smad2 and Smad3, which is a necessary step for TGF-β signaling activation. Thus, our study reveals a pro-oncogenic role of UBE2D1 in the progression of BC and may provide novel strategies for BC treatment.

Circular ribonucleic acids (RNAs) (circRNAs) are formed by covalently linking the downstream splice donor and the upstream splice acceptor. One of the most important functions of circRNAs is mainly exerted through binding RNA-binding proteins (RBPs). However, there is no efficient algorithm for identifying genome-wide circRNA-RBP interactions. Here, we developed a unique algorithm, circRIP, for identifying circRNA-RBP interactions from RNA immunoprecipitation sequencing (RIP-Seq) data. A simulation test demonstrated the sensitivity and specificity of circRIP. By applying circRIP, we identified 95 IGF2BP3-binding circRNAs based on the IGF2BP3 RIP-Seq dataset. We further identified 2823 and 1333 circRNAs binding to >100 RBPs in K562 and HepG2 cell lines, respectively, based on enhanced cross-linking immunoprecipitation (eCLIP) data, demonstrating the significance to survey the potential interactions between circRNAs and RBPs. In this study, we provide an accurate and sensitive tool, circRIP (https://github.com/bioinfolabwhu/circRIP), to systematically identify RBP and circRNA interactions from RIP-Seq and eCLIP data, which can significantly benefit the research community for the functional exploration of circRNAs.

N6 methyladenine (m6A) was the most abundant RNA internal modification in eukaryotic cells. It has been widely reported that abnormal regulation of m6A participates in the occurrence and development of malignant tumors. However, the current research mainly focused on the role of m6A methylation in post transcriptional regulation. Recently, many studies have shown that METTL3 was involved in transcriptional regulation at the transcriptional level by binding active chromatin, which provides a new direction for the study of m6A methylation in cancer.c-MYC was an oncogenic transcription factor that promotes tumorigenesis by activating and repressing its target genes that control the cell growth and proliferation. Triple negative breast cancer (TNBC) expressed high levels of the c-MYC oncogene product compared to other breast cancer subtypes.Inspired by the above, our study focused on the regulation of the target gene of the interaction between METTL3 and oncogenic transcript factors c-MYC, and then participates in the invasive progress of triple negative breast cancer. Our research suggested that METLL3 could bind to the transcription factor c-MYC, thereby regulating the target gene transcription of c-MYC.Funding Information: Our study was supported by “Basic and Clinical Medical Research Joint Fund of Zhongnan Hospital of Wuhan University (Grant No. JCZN2022008)” and “Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University (Grant No. ZNJC202236)”Declaration of Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.Ethics Approval Statement: The crosstalk between METTL3 and oncogenic transcript factors c-MYC in triple negative breast cancer: not just m6A modification. In this project, cancer and adjacent tissues of breast cancer patients fromZhongnanHospital of Wuhan University were collected (tissues used for immunofluorescence were fixed with 4% formaldehyde and stored, and the remaining tissues were frozenin liquid nitrogen), medical records were collected and clinical data of patients wereobtained. Informed consent of patients was obtained before obtaining clinical data andspecimens, and approval of Medical Ethics Committee of Wuhan University was obtained (Approval number: 2022009k).

Abstract The significant function of circRNAs in cancer was recognized in recent work, so a well-organized resource is required for characterizing the interactions between circRNAs and other functional molecules (such as microRNA and RNA-binding protein) in cancer. We previously developed cancer-specific circRNA database (CSCD), a comprehensive database for cancer-specific circRNAs, which is widely used in circRNA research. Here, we updated CSCD to CSCD2 (http://geneyun.net/CSCD2 or http://gb.whu.edu.cn/CSCD2), which includes significantly more cancer-specific circRNAs identified from a large number of human cancer and normal tissues/cell lines. CSCD2 contains >1000 samples (825 tissues and 288 cell lines) and identifies a large number of circRNAs: 1 013 461 cancer-specific circRNAs, 1 533 704 circRNAs from only normal samples and 354 422 circRNAs from both cancer and normal samples. In addition, CSCD2 predicts potential miRNA–circRNA and RBP–circRNA interactions using binding motifs from >200 RBPs and 2000 microRNAs. Furthermore, the potential full-length and open reading frame sequence of these circRNAs were also predicted. Collectively, CSCD2 provides a significantly enhanced resource for exploring the function and regulation of circRNAs in cancer.