Targeted silencing of MYCL1 by RNA interference inhibits migration and invasion of MGC-803 gastric cancer cells.

MYCL1 protein expression encoded by a proto-oncogene MYCL1, a member of the MYC family, is correlated with poor prognosis in gastric cancer patients. Nevertheless, the role of MYCL1 in gastric cancer cells remains unknown. In this study, the expression levels of MYCL1 mRNA and protein were downregulated by lentiviral-mediated RNA interference (RNAi) in the MGC-803 gastric cancer cell line. Then, the influence of MYCL1 on the biological behaviour of gastric cancer cells was investigated. Finally, a stable animal model of the MGC-803 human gastric cancer tumour model in nude mice was made successfully. Functionally, silencing of MYCL1 inhibited migration and invasion of the MGC-803 line in vitro and was accompanied with some ultrastructural changes. These results provide some evidences that lentiviral-mediated MYCL1 silencing may be a novel therapeutic strategy for the treatment of gastric cancer. SIGNIFICANCE OF THE STUDY: Gastric cancer is one of the most common malignant tumours worldwide and the second leading cause of cancer-related death in China. Our previous study revealed that expression of MYCL1 in gastric cancer tissue was associated with poor prognosis of patients. However, the potential underlying mechanism is still unclear. In the current study, we displayed the influence of MYCL1 gene on invasion and migration phenotype of gastric cancer cells and provided a possible explanation from the aspect of structural alteration. Our results suggested that downregulation of MYCL1 may be a potential therapeutic strategy for gastric cancer.

Expression and prognostic value of Mycl1 in gastric cancer.

As a member of the Myc proto-oncogene family, MYCL1 has been found to be amplified and overexpressed in some malignancies. However, the clinical significance of Mycl1 expression in gastric cancer is still unknown. Mycl1 expression was detected on tissue microarrays of gastric cancer samples in 176 cases using immunohistochemical staining, and its association with clinicopathological factors and overall survival was also analyzed. Mycl1 showed greater expression in gastric cancer tissue than in adjacent normal tissue (62.5% vs 46.0%, respectively, P=0.002), and its expression was correlated with patient age, tumor differentiation, and TNM stage (P=0.007, 0.003, and 0.002, respectively). The Mycl1 positive group had an unfavorable outcome compared with the negative group (P<0.001). Multivariate analysis showed that Mycl1 expression was an independent prognostic factor of gastric cancer (P=0.009). These results suggest that Mycl1 expression might be useful as a biomarker to predict prognosis and is a promising therapeutic target for patients with gastric cancer.

MYCL1 Amplification and Expression of L-Myc and c-Myc in Surgically Resected Small-Cell Lung Carcinoma.

Purpose: The Myc family, especially C-MYC and MYCL1, has been found involved in small-cell lung carcinoma (SCLC). Identification of the frequency of C-MYC and MYCL1 expression among SCLC patients may help to identify potential targets for therapeutic intervention. Our aim was to detect MYCL1 amplification, L-Myc and c-Myc expression, and investigate clinicopathological characteristics and survival status in patients with surgically resected SCLC. Methods: MYCL1 amplification was detected using fluorescence in situ hybridization (FISH), while L-Myc and c-Myc protein expressions were determined using immunohistochemistry (IHC) in the primary tumors of 46 resected SCLC patients. Results: Among the 46 evaluated specimens, MYCL1 amplification was identified in 3/46 cases (6.5%). One of the positive cases was MYCL1 gene amplification combined with fusion. 3/46 (6.5%) was positive for L-myc protein expression, and 4/46 (8.7%) was positive for c-Myc protein expression. Conclusion: Our study firstly multidimensional explored the expression of MYCL1 amplification, L-Myc and c-Myc protein and investigated clinicopathological characteristics and survival status in patients with surgically resected SCLC, which makes a contribution to subsequent research and therapeutic strategies.

Gender-specific transcriptional profiling of marine medaka (Oryzias melastigma) liver upon BDE-47 exposure.

Marine medaka (Oryzias melastigma) were exposed to 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) to investigate the gender-specific transcriptional profiles of liver tissue in response to this flame retardant. A cDNA library of O. melastigma was constructed, and 2304 clones were amplified from the library to fabricate a cDNA microarray. Sequences of these genes were assembled into 1800 sequences using Geneious, a bioinformatics software. Corresponding expressed sequence tags were blasted against the National Centre for Biotechnology Information non-redundant database and further classified into various biological categories according to the Gene Ontology project. Male and female three-month-old were fed a diet of BDE-47 contaminated Artemia at low dosage (290.3±172.3ng BDE-47/day) and high dosage (580.5±344.6ng BDE-47/day) for 5 and 21 days, respectively. The transcriptional profiles of O. melastigma liver were then generated by the species-specific cDNA microrarray. The results from microarray analysis suggested very different gene expression patterns between males and females for both BDE-47 exposure-dose and exposure-time, with male livers having stronger gene regulatory responses than female livers. Importantly, our results revealed that in male O. melastigma only, BDE-47 exposure may activate phosphoinositide-3-kinase and mitogen-activated protein kinase, proteins that play importance roles in cell growth, proliferation and survival.

Detection of gene amplification in MYCN, C-MYC, MYCL1, ERBB2, EGFR, AKT2, and human papilloma virus in samples from cervical smear normal cytology, intraepithelial cervical neoplasia (CIN I, II, III), and cervical cancer / Detección de amplificación en los genes MYCN, C-MYC, MYCL1, ERBB2, EGFR y AKT2 y del virus de papiloma humano en muestras de cepillado cervical en mujeres con citología normal y con neoplasia intraepitelial cervical (NIC) I, II, III y cáncer de cuello uterino

Introduction: Cervical cancer is the second most common cancer among women worldwide and the second cause of cancer mortality in women. It has been demonstrated that the process of cervical carcinogenesis displays genetic and environmental epigenetic components. Currently, research is focused on new prognosis markers like oncogene amplification.Objectives: To perform detection of MYCN, C-MYC, MYCL1, ERBB2, EGFR, and AKT2 amplification. Additionally, to detect human papillomavirus in samples from normal cytology smear, cervical intraepithelial neoplasia (CIN) I, II, and III and cervical cancer patients.Methods: Papillomavirus (HPV) genotyping by reverse line blot (RLB) performed and gene amplification by detection with real-time PCR with Taqman probes.Results: HPV was present in 4% of the patients with normal cytology, 48% in CIN I, 63.6% in CIN II, 64% in CIN III, and 70.8% in cervical cancer. Genes amplified in cervical cancer were MYCN (39.1%), ERBB2 (34.7%), and MYCL1 (30.4%); showed higher amplification in high-grade lesions and cervical cancer in relation to low-grade lesions and normal cytology with statistically significant differences. Besides the genes, C-MYC, EGFR, and AKT2 were amplified in samples from patients with cervical cancer by 12%, 18%, and 13%, respectively; we did not find statistical differences.Conclusion: Higher prevalence of gene amplification and HPV was found in high-grade cervical lesions and cervical cancer.

Introducción: El cáncer cervical es el segundo cáncer más importante en mujeres a nivel mundial y es la segunda causa de muerte por cáncer en mujeres. Se ha demostrado que el proceso de carcinogénesis cervical presenta componentes tanto genéticos como epigenéticos y medio ambientales. En la actualidad, hay gran interés en la búsqueda de marcadores moleculares asociados con la progresión de esta enfermedad, uno de los posibles mecanismos y que además está poco estudiado en cáncer cervical es la amplificación génica de algunos oncogenes como la familia MYC, EGFR y AKT entre otros.Objetivos: Detectar la amplificación génica de MYCN, C-MYC, MYCL1, ERBB2, EGFR y AKT2 además de la presencia del virus de papiloma humano en cepillados cervicales en mujeres con citología normal o con neoplasia intraepitelial cervical (NIC) I, II y III o con cáncer cervical.Métodos: Se genotipificó mediante reverse line blot (RLB) el virus de papiloma humano (VPH) y se determinó el estado de amplificación génica de los genes mencionados mediante PCR en tiempo real utilizando sondas taqman.Resultados: El VPH se encontró presente en 4% de las pacientes con citología normal, en 48% en NIC I, 63.6% en NIC II, 64% en NIC III y 70.8% en cáncer cervical. Los genes MYCN, MYCL1 y ERBB2 mostraron mayor amplificación en lesiones de alto grado y cáncer con diferencias estadísticamente significativas a las lesiones de bajo grado y citología normal, en 39.1%, 34.7% y 30.4% respectivamente. Además, se encontraron amplificados los genes C-MYC, EGFR y AKT2, en muestras de pacientes con cáncer cervical, en 12%, 18% y 13% respectivamente. Sin embargo, no se observaron diferencias estadísticamente significativas con respecto a las lesiones de alto y bajo grado y citología normal.Conclusión: En las lesiones de alto grado como en cáncer cervical, se encuentra mayor prevalencia del virus al igual que se detectan mayor cantidad de alteraciones genéticas como la amplificación génica.