While predicting the secondary structure of RNA is vital for researching its function, determining RNA secondary structure is challenging, especially for that with pseudoknots. Typically, several excellent computational methods can be utilized to predict the secondary structure (with or without pseudoknots), but they have their own merits and demerits. These methods can be classified into two categories: the multi-sequence method and the single-sequence method. The main advantage of the multi-sequence method lies in its use of the auxiliary sequences to assist in predicting the secondary structure, but it can only successfully predict in the presence of multiple highly homologous sequences. The single-sequence method is associated with the major merit of easy operation (only need the target sequence to predict secondary structure), but its folding parameters are the common features of diversity RNA, which cannot describe the unique characteristics of RNA, thus potentially resulting in the low prediction accuracy in some RNA. In this paper, “DMfold,” a method based on the Deep Learning and Improved Base Pair Maximization Principle, is proposed to predict the secondary structure with pseudoknots, which fully absorbs the advantages and avoids some disadvantages of those two methods. Notably, DMfold could predict the secondary structure of RNA by learning similar RNA in the known structures, which uses the similar RNA sequences instead of the highly homogeneous sequences in the multi-sequence method, thereby reducing the requirement for auxiliary sequences. In DMfold, it only needs to input the target sequence to predict the secondary structure. Its folding parameters are fully extracted automatically by deep learning, which could avoid the lack of folding parameters in the single-sequence method. Experiments show that our method is not only simple to operate, but also improves the prediction accuracy compared to multiple excellent prediction methods. A repository containing our code can be found at https://github.com/linyuwangPHD/RNA-Secondary-Structure-Database.

Mounting evidence suggests that long noncoding RNAs (lncRNAs) play important roles in the regulation of gene expression by acting as competing endogenous RNA (ceRNA). However, the regulatory mechanisms of lncRNA as ceRNA in gastric cancer (GC) are not fully understood. Here, we first constructed a dysregulated lncRNA-associated ceRNA network by integrating analysis of gene expression profiles of lncRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs). Then, we determined three lncRNAs (RP5-1120P11, DLEU2, and DDX11-AS1) as hub lncRNAs, in which associated ceRNA subnetworks were involved in cell cycle-related processes and cancer-related pathways. Furthermore, we confirmed that the two lncRNAs (DLEU2 and DDX11-AS1) were significantly upregulated in GC tissues, promote GC cell proliferation, and negatively regulate miRNA expression, respectively. The hub lncRNAs (DLEU2 and DDX11-AS1) could have oncogenic functions, and act as potential ceRNAs to sponge miRNA. Our findings not only provide novel insights on ceRNA regulation in GC, but can also provide opportunities for the functional characterization of lncRNAs in future studies.

Objective: Long non‐coding RNA (lncRNA) has become an important regulator of many human malignancies. However, the biological role and clinical significance of most lncRNA in gastric cancer (GC) remain unclear.Methods: We investigate the biological function, mechanism of action and clinical expression of lncRNA MYOSLID in GC. First, we analysed the differential expression of lncRNA MYOSLID in GC tissues and non‐cancerous tissues by analysing the sequencing data obtained from The Cancer Genome Atlas. Subsequently, we verified that lncRNA MYOSLID regulates the proliferation and apoptosis of GC cells by acting as a ceRNA against miR‐29c‐3p. The nude mouse xenograft was used to further confirm the functional significance of lncRNA MYOSLID in vivo.Results: We found for the first time that the expression of lncRNA MYOSLID was significantly up‐regulated in GC tissues, and the up‐regulation of lncRNA MYOSLID in GC was correlated with tumour size, AJCC stage, depth of invasion and survival time. In addition, apoptosis and growth arrest can be induced in vitro after knockdown of lncRNA MYOSLID, which inhibits tumorigenesis in mouse xenografts in vivo. Further in‐depth studies revealed that lncRNA MYOSLID acts as a ceRNA of miR‐29c‐3p, resulting in de‐repression of its downstream target gene MCL‐1.Conclusion: The lncRNA MYOSLID‐miR‐29c‐3p‐MCL‐1 axis plays a key role in the development of GC. Our findings may provide potential new targets for the diagnosis and treatment of human GC.

Fewer than 30% of patients with hepatocellular carcinoma (HCC) are eligible to receive curative therapies, and so a better understanding of the molecular mechanisms of HCC is needed to identify potential therapeutic targets. The role of microRNA (miRNA) in modulating tumour progression has been demonstrated, and therapies targeting miRNA appear promising. miR‐204‐5p has been shown to function in numerous types of cancer, but its role in HCC remains unclear. In this study, we found that miR‐204‐5p expression was downregulated in cancerous HCC tissues compared to nontumour tissues. Kaplan–Meier survival curve analysis also showed that low expression of miR‐204‐5p predicted worse outcomes of HCC patients. In addition, miR‐204‐5p expression was significantly lower in HCC cell lines. The function of miR‐204‐5p was also assessed both in vitro and in vivo. We demonstrated that ectopic expression of miR‐204‐5p in HCC cell lines inhibited HCC cell proliferation and clonogenicity using CCK8, BrdU and colony‐forming assays, while the inhibition of miR‐204‐5p enhanced proliferation and clonogenicity. Further in vivo studies in mice further confirmed the proliferation capacity of miR‐204‐5p. We also identified sine oculis homeobox homologue 1 (SIX1) as a direct target of miR‐204‐5p and showed that it was inversely correlated with miR‐204‐5p in both human and mouse HCC tissues. Transfection of miR‐204‐5p mimics in BEL‐7404 cells blocked the cell cycle by inhibiting the expression of cyclin‐D1 and cyclin‐A1, cell cycle‐related factors regulated by SIX1. More importantly, overexpression of the 3′UTR mutant SIX1 but not the wild‐type SIX1 abolished the suppressive effect of miR‐204‐5p, and downregulated SIX1 in BEL‐7402 cells that transfected with miR‐204 inhibitors could partly block the inhibitory effect of miR‐204‐5p on proliferation. Thus, we have demonstrated that miR‐204‐5p suppresses HCC proliferation by directly regulating SIX1 and its downstream factors.

It has been found that microRNAs (miRNAs) can function as a regulatory factor across species. For example, food-derived plant miRNAs may pass through the gastrointestinal (GI) tract, enter into the plasma and serum of mammals, and interact with endogenous RNAs to regulate their expression. Although this new type of regulatory mechanism is not well understood, it provides a fresh look at the relationship between food consumption and physiology. To investigate this new type of mechanism, we conducted a systematic computational study to analyze the potential functions of these dietary miRNAs in the human body. In this paper, we predicted human and plant target genes using RNAhybrid and set some criteria to further filter them. Then we built the cross-species regulatory network according to the filtered targets, extracted central nodes by PageRank algorithm and built core modules. We summarized the functions of these modules to three major categories: ion transport, metabolic process and stress response, and especially some target genes are highly related to ion transport, polysaccharides and the lipid metabolic process. Through functional analysis, we found that human and plants have similar functions such as ion transport and stress response, so our study also indicates the existence of a close link between exogenous plant miRNA targets and digestive/urinary organs. According to our analysis results, we suggest that the ingestion of these plant miRNAs may have a functional impact on consuming organisms in a cross-kingdom way, and the dietary habit may affect the physiological condition at a genetic level. Our findings may be useful for discovering cross-species regulatory mechanism in further study.

Gastric cancer (GC) is a considerable global health burden. Accumulating evidence suggests that long non-coding RNAs (lncRNAs) are aberrantly expressed in many cancers and play important roles in GC. However, only a few lncRNAs have been functionally characterized. In this study, we identified that long intergenic non-protein coding RNA 941 (LINC00941) is a potential biomarker for diagnosis and prognosis from the cancer genome atlas (TCGA), and we found that the expression of LINC00941 is associated with tumor depth and distant metastasis in GC. Furthermore, functional enrichment analysis of LINC00941 co-expression network demonstrated that LINC00941 might be an essential regulator of tumor metastasis and cancer cell proliferation. To validate our findings, we utilized the loss-of-function analysis to reveal the biological function of LINC00941 in GC cells. Loss-of-function analysis revealed that silence of LINC00941 inhibits GC cells proliferation, migration, and invasion in vitro and modulates tumor growth in vivo. Our findings confirmed that LINC00941 plays an important oncogenic function in GC and may serve as a potential biomarker for diagnosis and prognosis of GC.