PTBP1 Promotes Growth, Migration and Invasion of Cholangiocarcinoma Cells by Regulating mRNA Alternative Splicing / 中国生物化学与分子生物学报

Cholangiocarcinoma (CCA) is a highly invasive type of cancer with insidious onset and high mortality. Polypyrimidine tract-binding protein 1 (PTBP1) is highly over-expressed in various types of tumor tissues, which contributes to cancer progression. But the role of PTBP1 in CCA has not been explored yet. In this study, we aim to investigate the function of PTBP1 in CCA. Therefore, we used publicly available data from the cancer genome atlas (TCGA) to evaluate the dysregulation of PTBP1 in CCA. The results showed that the PTBP1 is significantly up-regulated in CCA tissues compared to the matched non-tumor tissues (P < 0. 05). We assessed the effects of PTBP1 on the growth of CCA cell lines RBE and HuH28 by performing CCK-8 and plate colony formation assays. The results showed that overexpression of PTBP1 significantly promoted the growth (P < 0. 01) of CCA cells, whereas knockdown of PTBP1 exhibited opposite effects. Transwell and Invasion assays revealed that overexpression of PTBP1 significantly promotes the migration and invasion of CCA cells (P < 0. 001), whereas knockdown of PTBP1 exhibited opposite effects (P < 0. 001). The RNA sequencing (RNA-seq) analysis in PTBP1-depleted cells showed that the up-regulated genes are significantly enriched in p53 signaling pathway, while the down-regulated genes are represented by cholesterol metabolism, Rho GTPase and TGF-β pathways. Then, the alternative splicing analysis revealed that inhibition of PTBP1 led to series of aberrant alternative splicing events, including several cancer-associated ones, such as splicing events within the TGF-β regulator TGIF1 and the p53 activity-correlated gene GNAS. These results indicate that PTBP1 promotes the progression of CCA likely by regulating the transcriptome alternative splicing to influence multiple cancer-associated signaling pathways.

Circulating microrna expression profiles in patients with stable and unstable angina

OBJECTIVES: High incidence and case fatality of unstable angina (UA) is, to a large extent, a consequence of the lack of highly sensitive and specific non-invasive markers. Circulating microRNAs (miRNAs) have been widely recommended as potential biomarkers for numerous diseases. In the present study, we characterized distinctive miRNA expression profiles in patients with stable angina (SA), UA, and normal coronary arteries (NCA), and identified promising candidates for UA diagnosis. METHODS: Serum was collected from patients with SA, UA, and NCA who visited the Department of Cardiovascular Diseases of the Meizhou People's Hospital. Small RNA sequencing was carried out on an Illumina HiSeq 2500 platform. miRNA expression in different groups of patients was profiled and then confirmed based on that in an independent set of patients. Functions of differentially expressed miRNAs were predicted using gene ontology classification and Kyoto Encyclopedia of Genes and Genomes pathway analysis. RESULTS: Our results indicated that circulating miRNA expression profiles differed between SA, UA, and NCA patients. A total of 36 and 161 miRNAs were dysregulated in SA and UA patients, respectively. miRNA expression was validated by reverse transcription quantitative polymerase chain reaction. CONCLUSION: The results suggest that circulating miRNAs are potential biomarkers of UA.

Transcriptome analysis of female and male flower buds of Idesia polycarpa Maxim. var. vestita Diels

Background: Idesia polycarpa Maxim. var. vestita Diels, a dioecious plant, is widely used for biodiesel due to the high oil content of its fruits. However, it is hard to distinguish its sex in the seedling stage, which makes breeding and production problematic as only the female tree can produce fruits, and the mechanisms underlying sex determination and differentiation remain unknown due to the lack of available genomic and transcriptomic information. To begin addressing this issue, we performed the transcriptome analysis of its female and male flower. Results: 28,668,977 and 22,227,992 clean reads were obtained from the female and male cDNA libraries, respectively. After quality checks and de novo assembly, a total of 84,213 unigenes with an average length of 1179 bp were generated and 65,972 unigenes (78.34%) could be matched in at least one of the NR, NT, Swiss-Prot, COG, KEGG and GO databases. Functional annotation of the unigenes uncovered diverse biological functions and processes, including reproduction and developmental process, which may play roles in sex determination and differentiation. The Kyoto Encyclopedia of Genes and Genomes pathway analysis showed many unigenes annotated as metabolic pathways, biosynthesis of secondary metabolites pathways, plant­ pathogen interaction, and plant hormone signal transduction. Moreover, 29,953 simple sequence repeats were identified using the microsatellite software. Conclusion: This work provides the first detailed transcriptome analysis of female and male flower of I. polycarpa and lays foundations for future studies on the molecular mechanisms underlying flower bud development of I. polycarpa.