长链非编码RNA的微RNA海绵作用与呼吸系统疾病

长链非编码RNA（long non-coding RNAs, lncRNAs）是一类由长度大于200个核苷酸组成的长链非编码序列。lncRNAs具有较长的序列,使得lncRNAs具有复杂的二级及三级结构,这也是lncRNAs结合DNA、RNA和蛋白质及其行使复杂功能的结构基础。MicroRNA（miRNAs)是长度在19到25个核苷酸之间的非编码单链RNA分子,是目前研究最多的小分子非编码RNA。而lncRNAs通过结合或者螯合miRNA来调节miRNA丰度,发挥lncRNA的“海绵”作用,从而调控一系列的病理生理过程。lncRNAs及miRNA在呼吸系统疾病的发生、发展、治疗和预后起重要作用。本文就lncRNAs及其“海绵”作用对呼吸系统疾病的影响及可能的机制进行综述。     

The latest progress on miR‐374 and its functional implications in physiological and pathological processes

Non‐coding RNAs (ncRNAs) have been emerging players in cell development, differentiation, proliferation and apoptosis. Based on their differences in length and structure, they are subdivided into several categories including long non‐coding RNAs (lncRNAs >200nt), stable non‐coding RNAs (60‐300nt), microRNAs (miRs or miRNAs, 18‐24nt), circular RNAs, piwi‐interacting RNAs (26‐31nt) and small interfering RNAs (about 21nt). Therein, miRNAs not only directly regulate gene expression through pairing of nucleotide bases between the miRNA sequence and a specific mRNA that leads to the translational repression or degradation of the target mRNA, but also indirectly affect the function of downstream genes through interactions with lncRNAs and circRNAs. The latest studies have highlighted their importance in physiological and pathological processes. MiR‐374 family member are located at the X‐chromosome inactivation center. In recent years, numerous researches have uncovered that miR‐374 family members play an indispensable regulatory role, such as in reproductive disorders, cell growth and differentiation, calcium handling in the kidney, various cancers and epilepsy. In this review, we mainly focus on the role of miR‐374 family members in multiple physiological and pathological processes. More specifically, we also summarize their promising potential as novel prognostic biomarkers and therapeutic targets from bench to bedside.     

Long noncoding RNAs biomarker-based cancer assessment

Cancer diagnosis have mainly relied on the incorporation of molecular biomarkers as part of routine diagnostic tool. The molecular alteration ranges from those involving DNA, RNA, noncoding RNAs (microRNAs and long noncoding RNAs [lncRNAs]) and proteins. lncRNAs are recently discovered noncoding endogenous RNAs that critically regulates the development, invasion, and metastasis of cancer cells. They are dysregulated in different types of malignancies and have the potential to serve as diagnostic markers for cancer. The expression of noncoding RNAs is altered following many diseases, and besides, some of them can be secreted from the cells into the circulation following the apoptotic and necrotic cell death. These secreted noncoding RNAs are known as cell free RNA. These RNAs can be secreted from the cell through the apoptotic body, extracellular vesicles including microvesicle and exosome, and bind to proteins. Since, lncRNAs display high organ and cell specificity, can be found in the blood, urine, tumor tissue, or other tissues or bodily fluids of some patients with cancer, this review summarizes the most significant and up-to-date findings of research on lncRNAs involvement in different cancers, focusing on the potential of cancer-related lncRNAs as biomarkers for diagnosis, prognosis, and therapy.     

Genome-wide differential expression of long noncoding RNAs and mRNAs in ovarian follicles of two different chicken breeds

Bashang long-tail chickens are an indigenous breed with dual purpose in China (meat and eggs) but have low egg laying performance. To improve the low egg laying performance, a genome-wide analysis of mRNAs and long noncoding RNAs (lncRNAs) from Bashang long-tail chickens and Hy-Line brown layers was performed. A total of 16,354 mRNAs and 8691 lncRNAs were obtained from ovarian follicles. Between the breeds, 160 mRNAs and 550 lncRNAs were found to be significantly differentially expressed. Integrated network analysis suggested some differentially expressed genes were involved in ovarian follicular development through oocyte meiosis, progesterone-mediated oocyte maturation, and cell cycle. The impact of lncRNAs on cis and trans target genes, indicating some lncRNAs may play important roles in ovarian follicular development. The current results provided a catalog of chicken ovarian follicular lncRNAs and genes for further study to understand their roles in regulation of egg laying performance.     

Nuclear hubs built on RNAs and clustered organization of the genome

RNAs play diverse roles in formation and function of subnuclear compartments, most of which are associated with active genes. NEAT1 and NEAT2/MALAT1 exemplify long non-coding RNAs (lncRNAs) known to function in nuclear bodies; however, we suggest that RNA biogenesis itself may underpin much nuclear compartmentalization. Recent studies show that active genes cluster with nuclear speckles on a genome-wide scale, significantly advancing earlier cytological evidence that speckles (aka SC-35 domains) are hubs of concentrated pre-mRNA metabolism. We propose the ‘karyotype to hub’ hypothesis to explain this organization: clustering of genes in the human karyotype may have evolved to facilitate the formation of efficient nuclear hubs, driven in part by the propensity of ribonucleoproteins (RNPs) to form large-scale condensates. The special capacity of highly repetitive RNAs to impact architecture is highlighted by recent findings that human satellite II RNA sequesters factors into abnormal nuclear bodies in disease, potentially co-opting a normal developmental mechanism.     

Long non-coding RNAs: Promising new targets in pulmonary fibrosis

Pulmonary fibrosis is characterized by progressive and irreversible scarring in the lungs with poor prognosis and treatment. It is caused by various factors, including environmental and occupational exposures, and some rheumatic immune diseases. Even the rapid global spread of the COVID-19 pandemic can also cause pulmonary fibrosis with a high probability. Functions attributed to long non-coding RNAs (lncRNAs) make them highly attractive diagnostic and therapeutic targets in fibroproliferative diseases. Therefore, an understanding of the specific mechanisms by which lncRNAs regulate pulmonary fibrotic pathogenesis is urgently needed to identify new possibilities for therapy. In this review, we focus on the molecular mechanisms and implications of lncRNAs targeted protein-coding and non-coding genes during pulmonary fibrogenesis, and systematically analyze the communication of lncRNAs with various types of RNAs, including microRNA, circular RNA and mRNA. Finally, we propose the potential approach of lncRNA-based diagnosis and therapy for pulmonary fibrosis. We hope that understanding these interactions between protein-coding and non-coding genes will contribute to the development of lncRNA-based clinical applications for pulmonary fibrosis.