Yuanyuan Gao

Many annotated long noncoding RNAs (lncRNAs) harbor predicted short open reading frames (sORFs), but the coding capacities of these sORFs and the functions of the resulting micropeptides remain elusive. Here, we report that human lncRNA MIR155HG encodes a 17-amino acid micropeptide, which we termed miPEP155 (P155). MIR155HG is highly expressed by inflamed antigen-presenting cells, leading to the discovery that P155 interacts with the adenosine 5'-triphosphate binding domain of heat shock cognate protein 70 (HSC70), a chaperone required for antigen trafficking and presentation in dendritic cells (DCs). P155 modulates major histocompatibility complex class II-mediated antigen presentation and T cell priming by disrupting the HSC70-HSP90 machinery. Exogenously injected P155 improves two classical mouse models of DC-driven auto inflammation. Collectively, we demonstrate the endogenous existence of a micropeptide encoded by a transcript annotated as "non-protein coding" and characterize a micropeptide as a regulator of antigen presentation and a suppressor of inflammatory diseases.

Under normal conditions, to achieve optimal spermatogenesis, the temperature of the testes should be 2–6 °C lower than body temperature. Cryptorchidism is one of the common pathogenic factors of male infertility. The increase of testicular temperature in male cryptorchidism patients leads to the disorder of body regulation and balance, induces the oxidative stress response of germ cells, destroys the integrity of sperm DNA, yields morphologically abnormal sperm, and leads to excessive apoptosis of germ cells. These physiological changes in the body can reduce sperm fertility and lead to male infertility. This paper describes the factors causing testicular heat stress, including lifestyle and behavioral factors, occupational and environmental factors (external factors), and clinical factors caused by pathological conditions (internal factors). Studies have shown that wearing tight pants or an inappropriate posture when sitting for a long time in daily life, and an increase in ambient temperature caused by different seasons or in different areas, can cause an increase in testicular temperature, induces testicular oxidative stress response, and reduce male fertility. The occurrence of cryptorchidism causes pathological changes within the testis and sperm, such as increased germ cell apoptosis, DNA damage in sperm cells, changes in gene expression, increase in chromosome aneuploidy, and changes in Na+/K+-ATPase activity, etc. At the end of the article, we list some substances that can relieve oxidative stress in tissues, such as trigonelline, melatonin, R. apetalus, and angelica powder. These substances can protect testicular tissue and relieve the damage caused by excessive oxidative stress.

According to the official statistics of the World Health Organization, at least 48 million couples and 186 million people suffer from infertility. Varicocele has been recognized as the leading cause of male infertility and can affect spermatogenesis and cause testicular and epididymal disorders through multiple diverse pathophysiological processes. Reactive oxygen species (ROS) produced by oxidative stress have been reconciled as an important pathogenic factor throughout the course of varicocele. Testis respond to heat stress, hypoxia, and inflammation at the cost of producing excessive ROS. High levels of ROS can lead to infertility not only through lipid peroxidation or DNA damage, but also by inactivating enzymes and proteins in spermatogenesis. This review studies the oxidative stress and its role in the pathophysiology and molecular biology of varicocele in the context of a decline in fertility.

Type 2 diabetes mellitus (T2DM) affects the formation of carotid atherosclerotic plaques (CAPs) and patients are prone to plaque instability. It is crucial to clarify transcriptomics profiles and identify biomarkers related to the progression of T2DM complicated by CAPs. Ten human CAP samples were obtained, and whole transcriptome sequencing (RNA-seq) was performed. Samples were divided into two groups: diabetes mellitus (DM) versus non-DM groups and unstable versus stable groups. The Limma package in R was used to identify lncRNAs, circRNAs, and mRNAs. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, protein-protein interaction (PPI) network creation, and module generation were performed for differentially expressed mRNAs. Cytoscape was used to create a transcription factor (TF)-mRNA regulatory network, lncRNA/circRNA-mRNA co-expression network, and a competitive endogenous RNA (ceRNA) network. The GSE118481 dataset and RT-qPCR were used to verify potential mRNAs.The regulatory network was constructed based on the verified core genes and the relationships were extracted from the above network. In total, 180 differentially expressed lncRNAs, 343 circRNAs, and 1092 mRNAs were identified in the DM versus non-DM group; 240 differentially expressed lncRNAs, 390 circRNAs, and 677 mRNAs were identified in the unstable versus stable group. Five circRNAs, 14 lncRNAs, and 171 mRNAs that were common among all four groups changed in the same direction. GO/KEGG functional enrichment analysis showed that 171 mRNAs were mainly related to biological processes, such as immune responses, inflammatory responses, and cell adhesion. Five circRNAs, 14 lncRNAs, 46 miRNAs, and 54 mRNAs in the ceRNA network formed a regulatory relationship. C22orf34-hsa-miR-6785-5p-RAB37, hsacirc_013887-hsa-miR-6785-5p/hsa-miR-4763-5p/hsa-miR-30b-3p-RAB37, MIR4435-1HG-hsa-miR-30b-3p-RAB37, and GAS5-hsa-miR-30b-3p-RAB37 may be potential RNA regulatory pathways. Seven upregulated mRNAs were verified using the GSE118481 dataset and RT-qPCR. The regulatory network included seven mRNAs, five circRNAs, six lncRNAs, and 14 TFs. We propose five circRNAs (hsacirc_028744, hsacirc_037219, hsacirc_006308, hsacirc_013887, and hsacirc_045622), six lncRNAs (EPB41L4A-AS1, LINC00969, GAS5, MIR4435-1HG, MIR503HG, and SNHG16), and seven mRNAs (RAB37, CCR7, CD3D, TRAT1, VWF, ICAM2, and TMEM244) as potential biomarkers related to the progression of T2DM complicated with CAP. The constructed ceRNA network has important implications for potential RNA regulatory pathways.

The World Health Organization predicts that infertility will be the third major health threat after cancer and cardiovascular disease, and will become a hot topic in medical research. Studies have shown that epigenetic changes are an important component of gametogenesis and related reproductive diseases. Epigenetic regulation of noncoding RNA (ncRNA) is appropriate and is a research hotspot in the biomedical field; these include long noncoding RNA (lncRNA), microRNA (miRNA), and PIWI-interacting RNA (piRNA). As vital members of the intracellular gene regulatory network, they affect various life activities of cells. LncRNA functions as a molecular bait, molecular signal and molecular scaffold in the body through molecular guidance. miRNAs are critical regulators of gene expression; they mainly control the stability or translation of their target mRNA after transcription. piRNA functions mainly through silencing genomic transposable elements and the post-transcriptional regulation of mRNAs in animal germ cells. Current studies have shown that these ncRNAs also play significant roles in the reproductive system and are involved in the regulation of essential cellular events in spermatogenesis and follicular development. The abnormal expression of ncRNA is closely linked to testicular germ cell tumors, poly cystic ovary syndrome and other diseases. This paper briefly presents the research on the reproductive process and reproductive diseases involving ncRNAs.