RESUMO
BACKGROUND Non-small-cell lung cancer (NSCLC) is predominant and has low 5-year relative survival rate. Therefore, the mechanisms of NSCLC tumorigenesis must be comprehensively elucidated. MicroRNA-323-3p (miR-323-3p) has been widely explored and found to exert functions in tumorigenesis of several cancer types. However, the expression pattern and biological function of miR-323-3p and the molecular mechanism underlying NSCLC development and progression remain unclear. MATERIAL AND METHODS Quantitative reverse-transcription polymerase chain reaction was used to detect the expression of miR-323-3p and TMEFF2 in NSCLC cell lines (A549, NCI-H3255, and H1299) and normal cell line (BEAS-2B). Methylthiazolyl tetrazolium, colony formation, and flow cytometry assays were performed to evaluate the effects of miR-323-3p and TMEFF2 on cell proliferation. Transwell assay was conducted to determine the effects of TMEFF2 on cell migration and invasion. Dual-luciferase reporter assay was used to verify whether TMEFF2 is a target of miR-323-3p. Western blot analysis was performed to analyze protein expression. RESULTS The expression of miR-323-3p increased in the 3 NSCLC cell lines (A549, NCI-H3255, and H1299). miR-323-3p regulated cellular progression by directly suppressing TMEFF2 expression and indirectly prohibited the activation of AKT and ERK pathways in NSCLC. CONCLUSIONS Overall, miR-323-3p was considered a lung cancer oncogene and could be a valuable target for NSCLC therapy.
Assuntos
Apoptose , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Sistema de Sinalização das MAP Quinases , Proteínas de Membrana/metabolismo , MicroRNAs/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células A549 , Apoptose/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Invasividade Neoplásica , Regulação para Cima/genéticaRESUMO
Triple-negative breast cancer (TNBC) is a complex breast cancer subtype characterized by the absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2). Long non-coding RNA (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) has been verified as oncogenic molecular in series of tumors, however, the role of ANRIL in TNBC carcinogenesis is still unclear. The purpose of present study is to investigate the expression and in-depth regulation of ANRIL on TNBC tumorigenesis. Expression level of ANRIL was up-regulated in TNBC tumor tissue and cell lines compared to noncancerous tissue and non-TNBC cells. Besides, the up-regulated ANRIL expression was closely correlated to poor prognosis. In vitro, loss-of-function experiments showed that ANRIL knockdown interfered by interference oligonucleotide could markedly suppress TNBC cells proliferation and enhance apoptosis. In vivo, ANRIL knockdown inhibited the tumor growth. Bioinformatics analysis and luciferase reporter assay revealed that miR-199a targeted ANRIL at 3'-UTR. Rescue experiments showed that miR-199a inhibitor could reverse the tumor-suppressing role of ANRIL knockdown on TNBC proliferation and apoptosis. Overall, present study demonstrated that ANRIL overexpression modulated TNBC tumorigenesis through acting as molecular 'sponge' for miR-199a, providing a novel insight and therapeutic target for TNBC.
Assuntos
Carcinogênese/metabolismo , MicroRNAs/biossíntese , RNA Longo não Codificante/biossíntese , Neoplasias de Mama Triplo Negativas/metabolismo , Idoso , Animais , Carcinogênese/genética , Carcinogênese/patologia , Proliferação de Células/fisiologia , Feminino , Células HEK293 , Humanos , Células MCF-7 , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Pessoa de Meia-Idade , RNA Longo não Codificante/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
Aim. To evaluate the influence of interval between neoadjuvant chemoradiotherapy (NCRT) and surgery on oncological outcome. Methods. A systematic search was conducted in PubMed, the Cochrane Library, and Embase databases for publications reporting oncological outcomes of patients following rectal cancer surgery performed at different NCRT-surgery intervals. Relative risk (RR) of pathological complete response (pCR) among different intervals was pooled. Results. Fifteen retrospective cohort studies representing 4431 patients met the inclusion criteria. There was a significantly increased rate of pCR in patients treated with surgery followed 7 or 8 weeks later (RR, 1.45; 95% CI, 1.18-1.78; and P < 0.01 and RR, 1.49; 95% CI, 1.15-1.92; and P = 0.002, resp.). There is no consistent evidence of improved local control or overall survival with longer or shorter intervals. Conclusion. Performing surgery 7-8 weeks after the end of NCRT results in the highest chance of achieving pCR. For candidates of abdominoperineal resection before NCRT, these data support implementation of prolonging the interval after NCRT to optimize the chances of pCR and perhaps add to the possibility of ultimate organ preservation.
