Expression of circular RNA hsa_circ_0014130 in lung adenocarcinoma cell lines and its effect on proliferation and invasion of lung adenocarcinoma cell line / 中华病理学杂志

Objective@#To investigate the function and mechanism of hsa_circ_0014130 in lung adenocarcinoma cell line and to find potential molecular inhibitors.@*Methods@#The hsa_circ_0014130 expression level detection and overexpression and subtraction experiments were performed using common cell lines of lung cancer (PC9, H1299, A549, HCC827, and BEAS-2B). qPCR was used to verify the proliferation and invasion of lung cancer cells by MTS and invasion assay, and then the targeted microRNA was searched through the database. Western blot was used to detect the downstream signaling pathways, and finally the effect of small molecule inhibitors was investigated on proliferation and invasion of non-small cell lung cancer.@*Results@#The expression level of hsa_circ_0014130 was up-regulated in the three cell lines, and both the overexpression plasmid and the subtractive siRNA were effectively transfected into the cells. Overexpression of hsa_circ_0014130 was able to promote the proliferation and invasion of tumor cells, and knockdown of hsa_circ_0014130 inhibited the proliferation and invasion of tumor cells. hsa_circ_0014130 was capable to target hsa-miR-566 to reduce its expression level and to inhibit epithelial-to-mesenchymal transition. The use of the small molecule inhibitor SB-431542 and simultaneous reduction of hsa_circ_0014130 significantly inhibited the proliferation and invasion of tumor cells.@*Conclusions@#The hsa_circ_0014130 promotes the invasion and proliferation of lung cancer cells by targeting hsa-miR-566 to enhance the expression of TWIST1, and its expression level can be significantly inhibited by the small molecule inhibitor SB-431542, which significantly inhibits the proliferation and invasion of lung cancer cells. Therefore,hsa_circ_0014130 is a potential lung cancer treatment target.

Aplicação de microRNAs na prática clínica / Application of microRNAs in the clinical practice

JUSTIFICATIVA E OBJETIVOS: A regulação da síntese proteica é essencial para o bom desempenho da função celular; um dos recursos usados no controle desse processo são os microRNAs, pequenos fragmentos de RNA que silenciam o RNA mensageiro. Portanto, mudanças na expressão dessas substâncias estão envolvidas na fisiopatologia de diversas doenças. Dessa forma, estudam-se maneiras de usar os microRNAs como ferramentas diagnósticas e terapêuticas. O objetivo deste estudo foi rever na literatura os microRNAs e suas perspectivas na área médica. CONTEÚDO: A biogênese dos microRNAs e sua aplicação na prática clínica, enfatizando a Oncologia, Psiquiatria e Cardiologia. CONCLUSÃO: Apesar de muitos microRNAs não terem sua função ainda estabelecida, o conhecimento do progresso já feito é fundamental para compreender os avanços terapêuticos e diagnósticos que estão se revelando.

BACKGROUND AND OBJECTIVES: The regulation of protein synthesis is essential for a good cellular function; one way to control this process is through microRNAs, small fragments of RNA which can silence the messenger RNA. Therefore, alterations on the expression of these molecules are involved in the pathophysiology of several diseases. Thus, ways to use microRNAs as diagnostic and therapeutic tools are being studied. The objective of the present study is to review literature on microRNA and its perspectives in medicine. CONTENTS : MicroRNAs biogenesis and its applications in the clinical practice, focusing on Oncology, Psychiatry and Cardiology. CONCLUSION: Even though many microRNAs function is not well established, the knowledge of the progress done is critical to understand the diagnostic and therapeutic advances that are being revealed.

Current trends in molecular classification of cancers / 中华检验医学杂志

Tumor morphology from the microscopic appearance has being served as the basis of tumor classification,but has serious 1imitations.Molecular aberrations,including DNA,RNA and protein,ale playing an ever increasing role in guiding classification,prognosis,and therapeutic strategies in cancer patients.A specific molecular profile correlating with important clinical parameters should allow physicians to base management decisions on the molecular characteristics of an individual patient's tumor.The application of high-throughput technologies to tumor,3 should make it possible to generate comprehensive molecular profiles.The integration of clinical,morphological and molecular data could result in a more precise classification of cancers,and lead to better understanding,individualized predicting and treatment,which would give the maximum benefit to the patients.

Análise comparativa dos transcritomas do córtex adrenal normal e adenocarcinoma do córtex adrenal / Comparative analysis of normal adrenal cortice and adrenocortical carcinoma transcriptomes

A carcinogênese do córtex da supra-renal é um processo complexo que envolve alterações genéticas múltiplas e sequenciais. Embora algumas dessas alterações já tenham sido caracterizadas, de modo geral estes mecanismos permanecem pouco compreendidos. Um conhecimento mais aprofundado dos mesmos não só levaria à descoberta de novos marcadores de prognóstico como também a alvos terapêuticos em potencial. A fim de melhor caracterizarmos os mecanismos envolvidos na progressão maligna do tumor e selecionarmos genes candidatos a serem marcadores de malignidade e alvos terapêuticos, nós estudamos os RNAs de uma linhagem celular derivada de um tumor adrenocortical maligno (NCI-H295A) e um espécime de tumor do córtex da supra-renal por "Differential Display" (DDRT-PCR). Foi selecionado um total de 317 transcritos únicos diferencialmente expressos, com base na análise densitométrica digital dos géis de DDRTPCR. A anotação funcional dos genes hiper-expressos mostrou relação com motilidade celular e proliferação. Entre os hipo-expressos foram identificados genes envolvidos na regulação de transcrição, síntese e processamento de RNA e remodelamento da cromatina. A expressão de dois genes entre os transcritos selecionados foi verificada por RT-PCR semi-quantitativa em 19 tumores adrenocorticais adultos e pediátricos, metastáticos e não metastáticos. Os genes da fucosiltransferase-11 e do supressor tumoral BCSC-1 (hiper- e hipo-regulado, respectivamente) encontraram-se diferencialmente expressos nos subgrupos específicos das 19 amostras tumorais. Em suma, o DDRT-PCR revelou-se uma ferramenta valiosa para uma análise global dos transcritomas do córtex da supra-renal e para selecionar genes com possível envolvimento na tumorigênese adrenocortical. Novos aspectos da biologia, progressão e possíveis alvos terapêuticos moleculares puderam ser vislumbrados.

There are important gaps in the present knowledge about adrenocortical tumorigenesis. For this reason we compared by Differential Display RNAs from a carcinoma-derived cell line (NCI-H295A) and a metastatic adrenocortical tumor and characterized 317 differentially expressed transcripts. The up-regulated genes are mainly related to cell motility and proliferation. Among the down-regulated genes, those involved in regulation of transcription, RNA synthesis and processing and chromatin remodeling were identified. Differential expression of FUTT11 and BCSC-1 tumor suppressor gene were confirmed in specific subsets of 19 adult and pediatric adrenocortical tumors and might serve as marker for malignancy. Our data revealed previously unknown aspects of adrenal tumorigenesis.