Weicheng Liang

BACKGROUND: Circular RNAs are a class of regulatory RNA transcripts, which are ubiquitously expressed in eukaryotes. In the current study, we evaluate the function of a novel circRNA derived from the β-catenin gene locus, circβ-catenin. RESULTS: Circβ-catenin is predominantly localized in the cytoplasm and displays resistance to RNase-R treatment. We find that circβ-catenin is highly expressed in liver cancer tissues when compared to adjacent normal tissues. Silencing of circβ-catenin significantly suppresses malignant phenotypes in vitro and in vivo, and knockdown of this circRNA reduces the protein level of β-catenin without affecting its mRNA level. We show that circβ-catenin affects a wide spectrum of Wnt pathway-related genes, and furthermore, circβ-catenin produces a novel 370-amino acid β-catenin isoform that uses the start codon as the linear β-catenin mRNA transcript and translation is terminated at a new stop codon created by circularization. We find that this novel isoform can stabilize full-length β-catenin by antagonizing GSK3β-induced β-catenin phosphorylation and degradation, leading to activation of the Wnt pathway. CONCLUSIONS: Our findings illustrate a non-canonical function of circRNA in modulating liver cancer cell growth through the Wnt pathway, which can provide novel mechanistic insights into the underlying mechanisms of hepatocellular carcinoma.

A series of pneumonia cases caused by 2019 novel coronavirus (2019-nCoV, also named COVID-19) are being reported globally. Based on recent publications,1–3 the most common symptoms in patients infected by 2019-nCoV were fever and cough. However, the incidence of other clinical features differs in different reports. To address this issue, we collected the data from three reports1–3 and compared the incidence accordingly. We found that the incidence of leucopenia, fever and diarrhoea in the three studies showed a statistically significant difference (table 1). Among these symptoms, diarrhoea displayed the smallest p-value (p=0.016), suggesting that the criteria for diagnosing diarrhoea may differ in different hospitals. Due to the different criteria, clinicians may underestimate the value of this symptom in clinical practice, and it may affect the preliminary diagnostic accuracy. View this table: Table 1 Intergroup comparison between three recent publications Recent studies showed that the spike protein of 2019-nCoV shared the same cell entry receptor ACE2 as SARS-CoV.4 5 In terms of the pathological importance of ACE2 in modulating intestinal inflammation and diarrhoea,6 we examined the expression profiles of ACE2 in various human tissues and found that ACE2 was highly expressed in the human small intestine (online supplementary file 1). Intriguingly, the RNA level of ACE2 was quite low in lung tissues from healthy donors.### Supplementary data [gutjnl-2020-320832supp001.pdf] Given that the distribution of ACE2 may determine the route of 2019-nCoV infection, we next evaluated the expression of ACE2 in different cell …

Bone homeostasis is tightly orchestrated and maintained by the balance between osteoblasts and osteoclasts. Recent studies have greatly expanded our understanding of the molecular mechanisms of cellular differentiation. However, the functional roles of non-coding RNAs particularly lncRNAs in remodeling bone architecture remain elusive. In our study, lncRNA H19 was found to be upregulated during osteogenesis in hMSCs. Stable expression of H19 significantly accelerated in vivo and in vitro osteoblast differentiation. Meanwhile, by using bioinformatic investigations and RIP assays combined with luciferase reporter assays, we demonstrated that H19 functioned as an miRNA sponge for miR-141 and miR-22, both of which were negative regulators of osteogenesis and Wnt/β-catenin pathway. Further investigations revealed that H19 antagonized the functions of these two miRNAs and led to de-repression of their shared target gene β-catenin, which eventually activated Wnt/β-catenin pathway and hence potentiated osteogenesis. In addition, we also identified a novel regulatory feedback loop between H19 and its encoded miR-675-5p. And miR-675-5p was found to directly target H19 and counteracted osteoblast differentiation. To sum up, these observations indicate that the lncRNA H19 modulates Wnt/β-catenin pathway by acting as a competing endogenous RNA, which may shed light on the functional role of lncRNAs in coordinating osteogenesis.

// Wei-ming Fu 2, * , Ying-fei Lu 2, 3, * , Bao-guang Hu 4 , Wei-cheng Liang 5 , Xiao Zhu 6 , Hai-di Yang 7 , Gang Li 3, 8 , Jin-fang Zhang 1, 3, 8 1 School of Medicine, South China University of Technology, Guangzhou 511458, P.R. China 2 Guangzhou Institute of Advanced Technology, Chinese Academy of Sciences, Guangzhou 511458, P.R. China 3 Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, P.R. China 4 Department of Gastrointestinal Surgery, The Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong, P.R. China 5 School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, P. R. China 6 Guangdong Province Key Laboratory of Medical Molecular Diagnosis, Guangdong Medical College, Dong guan, 523808, P.R. China 7 Department of Otolaryngology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, P.R. China 8 Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, P.R. China * These authors contributed equally to this work Correspondence to: Jin-fang Zhang, e-mail: zhangjf06@cuhk.edu.hk Keywords: Hotair, angiogenesis, nasopharyngeal carcinoma, GRP78 Received: July 10, 2015      Accepted: November 25, 2015      Published: December 22, 2015 ABSTRACT Nasopharyngeal carcinoma (NPC), as a unique head and neck cancer type, is particularly prevalent in certain geographic areas such as eastern Asia. Until now, the therapeutic options have been restricted mainly to radiotherapy or chemotherapy. However, the clinical treatment effect remains unsatisfactory even if the combined radio-chemotherapies. Therefore, it is urgently needed to develop effective novel therapies against NPC. In this study, we discovered that lncRNA Hotair was extremely abundant in NPC cells and clinical NPC samples. Further studies showed that Hotair knockdown significantly attenuated both in vitro and in vivo tumor cell growth and angiogenesis. Our study also demonstrated that Hotair promoted angiogenesis through directly activating the transcription of angiogenic factor VEGFA as well as through GRP78-mediated upregulation of VEGFA and Ang2 expression. Therefore, Hotair may serve as a promising diagnostic marker and therapeutic target for NPC patients.