Diffuse gliomas are well known malignant brain tumors. Long non-coding RNAs (lncRNAs), a type of RNA transcript with more than 200 nucleotides, involve in tumorigenesis and development of various cancers. This study focused on identifying differentially expressed lncRNAs in gliomas based on gene expression profiling, and chose certain lncRNAs PVT1, CYTOR, HAR1A and MIAT, which changed with significant differences. Further analysis of TCGA and GEO data revealed that the expressions of PVT1 and CYTOR were up-regulated, while HAR1A and MIAT expressions were down-regulated in gliomas. Their expression patterns were validated in an independent cohort containing 98 glioma specimens and 12 non-tumor tissue controls. High expression of PVT1 and CYTOR as well as low HAR1A and MIAT expression were associated with high Ki-67 level and more TP53 mutation. Kaplan-Meier survival curve and Cox regression analyses showed that glioma patients with high PVT1 expression or low HAR1A expression had poor survival outcome, aberrantly expressed PVT1 and HAR1A could be the independent prognosis biomarkers for glioma patients. Moreover, down-regulation of PVT1 and up-regulation of HAR1A contributed to improve the survival of patients who received chemotherapy and radiotherapy. These results implied that these four lncRNAs might play important role in diffuse gliomas progression, particularly, PVT1 and HAR1A could be explored as promising biomarkers for diagnosis, prognosis and target therapy of diffuse gliomas.

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The transcriptome is the complete set of transcripts for certain type of cells or tissues in a specific developmental stage or physiological condition. Transcriptome analysis can provide a comprehensive understanding of molecular mechanisms involved in specific biological processes and diseases from the information on gene structure and function. Transcriptome has been challenging due to the efficient and fast procedures of RNA-seq. RNA-seq, refers to the use of high-throughput sequencing technologies to sequence cDNA library transcribed from all RNAs in tissues or cells, can be used to quantify, profile, and discover RNA transcripts by sequence reads. Thus, the transcripts can then be mapped on the reference genome to get comprehensive genetic information, such as transcription localization and alternative splicing status. RNA-Seq has been widely used in biological, medical, clinical and pharmaceutical research. The detailed principles, technical characteristics and applications of RNA-seq are reviewed here, and the challenges and application potentials of RNA-seq in the future are also discussed. This will present the useful information for other researchers.

Inner Mongolia and Liaoning cashmere goats in China are well-known for their cashmere quality and yield. Thus, they are great models for identifying genomic regions associated with cashmere traits. Herein, 53 Inner Mongolia cashmere goats, Liaoning cashmere goats and Huanghuai goats were genotyped, and 53,347 single-nucleotide polymorphisms (SNPs) were produced using the Illumina Caprine 50K SNP chip. Additionally, we identified some positively selected SNPs by analyzing Fst and XP-EHH. The top 5% of SNPs had selection signatures. After gene annotation, 222 and 173 candidate genes were identified in Inner Mongolia and Liaoning cashmere goats, respectively. Several genes were related to hair follicle development, such as TRPS1, WDR74, LRRC14, SPTLC3, IGF1R, PADI2, FOXP1, WNT10A and CSN3. Gene enrichment analysis of these cashmere trait-associated genes related 67 enriched signaling pathways that mainly participate in hair follicle development and stem cell pluripotency regulation. Furthermore, we identified 20 overlapping genes that were selected in both cashmere goat breeds. Among these overlapping genes, WNT10A and CSN3, which are associated with hair follicle development, are potentially involved in cashmere production. These findings may improve molecular breeding of cashmere goats in the future.

Wnt/β-catenin signaling is essential for proliferation and maintenance of cancer stem cell-like traits of various cancer cells. In non-small-cell lung carcinoma (NSCLC), the mechanisms underlying the hyperactivation of Wnt signaling remain unclear, as mutations in APC and β-catenin genes are rare in NSCLC. RIF1 has been shown upregulated in breast and cervical cancer, this study intends to find out the potential effects of the expression and biological functions of RIF1 in NSCLC. Here we revealed that RIF1 was highly expressed in NCSLC at both mRNA and protein levels. RIF1 expression was significantly associated with clinical stage (P < 0.05) and prognosis (P < 0.001) of NSCLC patients. RIF1 knockdown inhibited NSCLC cell growth in vitro and in vivo, whereas overexpression of RIF1 in NSCLC cell lines promoted cell growth, cell cycle progression and cancer stem cell (CSC)-like properties via promoting PP1–AXIN interaction and thereby activating Wnt/β-catenin signaling. Inhibition of PP1 in RIF1-overexpressed cells counteracted the effects of RIF1 on cell growth and CSC-like phenotype, as well as the Wnt/β-catenin signaling. RIF1 expression was positively correlated with β-catenin at the protein level in 32 NSCLC tissues. RIF1 expression closely related to MYC (r = 0.28, P < 0.001) and CCND1 (r = 0.14, P < 0.01) expression at the mRNA level in cohorts of The Cancer Genome Atlas (TCGA). These results indicated that RIF1 had an oncogenic role as a novel positive regulator of Wnt/β-catenin signaling by directing PP1 to dephosphorylate AXIN; this novel mechanism may present a new therapeutic target for NSCLC.

Tibetan goat is an ancient breed, which inhabits the adverse conditions of the plateaus in China. To investigate the role of selection in shaping its genomes, we genotyped Tibetan goats (Nagqu Prefecture, above 4500 m) and three lowland populations (Xinjiang goats, Taihang goats and Huanghuai goats). The result of PCA, neighbor-joining (N-J) tree and model-based clustering showed that the genetic structure between the Tibetan goat and the three lowland populations has significant difference. As demonstrated by the di statistic, we found that some genes were related to the high-altitude adaptation of Tibetan goats. Functional analysis revealed that these genes were enriched in the VEGF (vascular endothelial growth factor) signaling pathway and melanoma, suggesting that nine genes (FGF2, EGFR, AKT1, PTEN, MITF, ENPEP, SIRT6, KDR, and CDC42) might have important roles in the high-altitude adaptation of Nagqu Tibetan goats. We also found that the LEPR gene was under the strongest selection (di value = 16.70), and it could induce upregulation of the hypoxic ventilatory response. In addition, five genes (LEPR, LDB1, EGFR, NOX4 and FGF2) with high di values were analyzed using q-PCR. Among them, we found that LEPR, LDB1 and FGF2 exhibited higher expression in the lungs of the Tibetan goats; LEPR, EGFR and LDB1 exhibited higher expression in the hearts of the Huanghuai goat. Our results suggest that LEPR, LDB1, EGFR and FGF2 genes may be related to the high-altitude adaptation of the goats. These findings improve our understanding of the selection of the high-altitude adaptability of the Nagqu Tibetan goats and provide new theoretical knowledge for the conservation and utilization of germplasm resources.

The aim of this study was to examine the correlation between the platelet-derived growth factor-D (PDGF-D) gene and sheep tail type character and explore the potential underlying mechanism. A total of 533 sheep were included in this study. Polymorphic sites were examined by Pool-seq, and individual genotype identification and correlation analysis between tail type data were conducted using the matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-TOF-MS) method. JASPART website was used to predict transcription factor binding sites in the promoter region with and without PDGF-D gene mutation. The effect of PDGF-D on adipogenic differentiation of sheep preadipocytes was investigated. Two single nucleotide polymorphism sites were identified: g.4122606 C > G site was significantly correlated with tail length, and g.3852134 C > T site was significantly correlated with tail width. g.3852134 C > T was located in the promoter region. Six transcription factor binding sites were eliminated after promoter mutation, and three new transcription factor binding sites appeared. Expression levels of peroxisome proliferator-activated receptor gamma (PPARγ) and lipoproteinlipase (LPL) were significantly up-regulated upon PDGF-D overexpression. Oil red O staining showed increased small and large oil drops in the PDGF-D overexpression group. Together these results indicate the PDGF-D gene is an important gene controlling sheep tail shape and regulating sheep tail fat deposition to a certain degree.

Replication timing regulatory factor 1 (RIF1) plays an important role in DNA replication regulation, stem cell pluripotency and DNA repair pathway. However, little is known about the molecular mechanisms and physiological significance of RIF1 in cancer and chemotherapy efficacy. In this study, we found that RIF1 is upregulated in cervical cancer tissues compared with normal tissues both at mRNA and protein levels through online databases. RIF1 knockdown reduced cervical cancer cell growth, colony formation, migration and epithelial–mesenchymal transition (EMT) markers. Flow cytometry analysis indicated that RIF1 knockdown induced apoptosis and G2 cell cycle arrest. Furthermore, RIF1 knockdown increased cisplatin sensitivity, cisplatin-induced G2/M phase arrest, apoptosis and led to defects in DNA repair in a concentration-dependent manner. In terms of mechanism research, increased CDKN1A expression and Bax/Bcl-2/caspase-3 signaling pathway might be involved in the G2/M phase arrest and increased apoptosis in RIF1-silenced cervical cancer cells. Thus, these findings indicate that RIF1 knockdown prior to chemotherapy may be a potential effective therapeutic strategy for cervical cancer.