Improved lung cancer classification by employing diverse molecular features of microRNAs.

MiRNAs are edited or modified in multiple ways during their biogenesis pathways. It was reported that miRNA editing was deregulated in tumors, suggesting the potential value of miRNA editing in cancer classification. Here we extracted three types of miRNA features from 395 LUAD and control samples, including the abundances of original miRNAs, the abundances of edited miRNAs, and the editing levels of miRNA editing sites. Our results show that eight classification algorithms selected generally had better performances on combined features than on the abundances of miRNAs or editing features of miRNAs alone. One feature selection algorithm, i.e., the DFL algorithm, selected only three features, i.e., the frequencies of hsa-miR-135b-5p, hsa-miR-210-3p and hsa-mir-182_48u (an edited miRNA), from 316 training samples. Seven classification algorithms achieved 100% accuracies on these three features for 79 independent testing samples. These results indicate that the additional information of miRNA editing is useful in improving the classification of LUAD samples.

Phased secondary small interfering RNAs in Camellia sinensis var. assamica.

Phased secondary small interfering RNAs (phasiRNAs) in plants play important roles in regulating genome stability, plant development and stress adaption. Camellia sinensis var. assamica has immense economic, medicinal and cultural significance. However, there are still no studies of phasiRNAs and their putative functions in this valuable plant. We identified 476 and 43 PHAS loci which generated 4290 twenty one nucleotide (nt) and 264 twenty four nt phasiRNAs, respectively. Moreover, the analysis of degradome revealed more than 35000 potential targets for these phasiRNAs. We identified several conserved 21 nt phasiRNA generation pathways in tea plant, including miR390 → TAS3, miR482/miR2118 → NB-LRR, miR393 → F-box, miR828 → MYB/TAS4, and miR7122 → PPR in this study. Furthermore, we found that some transposase and plant mobile domain genes could generate phasiRNAs. Our results show that phasiRNAs target genes in the same family in cis- or trans-manners, and different members of the same gene family may generate the same phasiRNAs. The phasiRNAs, generated by transposase and plant mobile domain genes, and their targets, suggest that phasiRNAs may be involved in the inhibition of transposable elements in tea plant. To summarize, these results provide a comprehensive view of phasiRNAs in Camellia sinensis var. assamica.

Identification of microRNA editing sites in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a malignant tumor originating from the renal tubular epithelium. Although the microRNAs (miRNAs) transcriptome of ccRCC has been extensively studied, the role of miRNAs editing in ccRCC is largely unknown. By analyzing small RNA sequencing profiles of renal tissues of 154 ccRCC patients and 22 normal controls, we identified 1025 miRNA editing sites from 246 pre-miRNAs. There were 122 editing events with significantly different editing levels in ccRCC compared to normal samples, which include two A-to-I editing events in the seed regions of hsa-mir-376a-3p and hsa-mir-376c-3p, respectively, and one C-to-U editing event in the seed region of hsa-mir-29c-3p. After comparing the targets of the original and edited miRNAs, we found that hsa-mir-376a-1_49g, hsa-mir-376c_48g and hsa-mir-29c_59u had many new targets, respectively. Many of these new targets were deregulated in ccRCC, which might be related to the different editing levels of hsa-mir-376a-3p, hsa-mir-376c-3p, hsa-mir-29c-3p in ccRCC compared to normal controls. Our study sheds new light on miRNA editing events and their potential biological functions in ccRCC.

Identification of microRNA editing sites in three subtypes of leukemia.

Leukemia is an aberrant hyper-proliferation of immature blood cells that do not form solid tumors. The transcriptomes of microRNAs (miRNAs) of leukemia have been intensively explored. However, miRNA editing of leukemia has not been extensively studied. To identify miRNA editing patterns and explore their functional relevance in leukemia, we analyzed 200 small RNA sequencing profiles of three subtypes of leukemia and identified hundreds of miRNA editing sites in three subtypes of leukemia. Then, we compared the editing levels of identified miRNA editing sites in leukemia and normal controls. Many miRNAs were differential edited in different subtypes of leukemia. We also found the editing levels of 3'-A editing sites of hsa-mir-21-5p and hsa-mir-155-5p decreased in chronic lymphocytic leukemia patients with radiation treatments. By integrating PAR-CLIP sequencing profiles, we predicted the targets of original and edited miRNAs. One of the edited miRNA, hsa-let-7b_5c, with an additional cytosine at 5' end of hsa-let-7b-5p, potentially targeted VBP1 and CTDSP1. CTDSP1 was significantly downregulated in T-ALL compared to normal controls, which might be originated from the hyperediting of hsa-let-7b-5p in T-ALL. Our study provides a comprehensive view of miRNA editing in three different subtypes of leukemia.

A novel bovine serum albumin and sodium alginate hydrogel scaffold doped with hydroxyapatite nanowires for cartilage defects repair.

Cartilage tissue engineering has become the trend of cartilage defect repair owing to the engineered biomimetic tissue that can mimic the structural, biological and functional characteristics of natural cartilage. Biomaterials with high biocompatibility and regeneration capacity are expected to be used in cartilage tissue engineering. Herein, in this study, a dual-network bovine serum albumin/sodium alginate with hydroxyapatite nanowires composite (B-S-H) hydrogel scaffold has been prepared for cartilage repair. The obtained B-S-H hydrogel scaffold exhibits ideal physical properties, such as excellent mechanical strength, high porosity and swelling ratio, as well as the excellent biological activity to promote the human bone marrow derived mesenchymal stem cells (hBMSCs) proliferation and differentiation. The in vivo study further shows that the B-S -H hydrogel scaffold can obviously promote the generation of new cartilage that integrates well with surrounding tissues and is similar to adjacent cartilage in terms of thickness. It is considered that the B-S-H hydrogel scaffold has great potential in the application of cartilage defects repair.