RESUMO
In tumor research, the occurrence and origin of tumors are the fundamental problems. In the 1970s, the basic discussion of the developmental biology problem of tumors was proposed, and it was believed that tumorigenesis is closely related to developmental biology. Tumors are abnormal biological structures in organisms, and their biological behavior is very similar to that of the early embryo. Many tumor-related genes also serve regulatory roles in the normal development and differentiation of embryos. However, it remains unclear whether gene expression in early embryos has any similarities with tumor cells. In this study, to compare the similarities and differences in gene expression between early embryos and tumor cells, reverse transcription-quantitative PCR was conducted to determine and compare the relative expression levels of nine tumor-related genes in the brain glioma cell line, T98G, and in the early embryo of Spodoptera litura, which is fast-growing, low-cost, easily accessible and easy to observe. The expression of tumor-related genes in early embryos and the similarity of regulatory mechanisms between early embryonic development and tumor growth were explored. In conclusion, tumor growth may be regarded as an abnormal embryogenic activation that happens in the organs of adult individuals.
RESUMO
The incidence and associated mortality of lung cancer in tin miners in Gejiu County and farmers in Xuanwei Country, Yunnan Province have been very high in the world. Current published literatures on the molecular mechanisms of lung cancer initiation and progression in Gejiu and Xuanwei County are still controversial. Studies confirmed that microRNA-34a (miR-34a) functioned as a vital tumor suppressor in tumorigenesis and progression. However, the role and precise mechanisms of miR-34a and its regulatory gene network in initiation and progression of lung cancer in Gejiu and Xuanwei County, Yunnan Province, have not been elucidated. In the current study, we first found that miR-34a was downregulated in Gejiu lung squamous carcinoma YTMLC-90, Xuanwei lung adenocarcinoma XWLC-05, and other non-small cell lung carcinoma (NSCLC) cell lines, and miR-34a overexpression inhibited cell proliferation, migration and invasion, as well as induced cell apoptosis in YTMLC-90 and XWLC-05 cells. Our findings revealed that miR-34a is critical and cannot be considered as the area-specific non-coding RNA in initiation and progression of lung cancer in Gejiu and Xuanwei County. Next we revealed that miR-34a overexpression suppressed lung cancer growth and metastasis partially via increasing PTEN but reducing CDK6 expression that might lead to subsequent inactivation of PI3K/AKT pathway. Furthermore, our findings demonstrated that YY1 functioned as a tumor suppressor gene in initiation and progression of lung cancer in Gejiu and Xuanwei County. In conclusion, our findings in the study confirmed that miR-34a overexpression could simultaneously suppress tumor growth and metastasis and play a vital role in tumorigenesis and progression of NSCLC via increasing PTEN and YY1 expression, but decreasing CDK6. Most interestingly, our findings also raised doubts about the current ideas about these area-specific diseases.
RESUMO
Lung cancer is the most prevalent and observed type of cancer in Xuanwei County, Yunnan, South China. Lung cancer in this area is called Xuanwei lung cancer. However, its pathogenesis remains largely unknown. To date, a number of studies have shown that microRNA (miR)218 functions as a tumor suppressor in multiple types of cancer. However, the role of miR218 and its regulatory gene network in Xuanwei lung cancer have yet to be investigated. The current study identified that the expression levels of miR218 in XWLC05 cells were markedly lower compared with those in immortalized lung epithelial BEAS2B cells. The present study also demonstrated that overexpression of miR218 could decrease cell proliferation, invasion, viability and migration in Xuanwei lung cancer cell line XWLC05 and NSCLC cell line NCIH157. Additionally, the results revealed that overexpression of miR218 could induce XWLC05 and NCIH157 cell apoptosis by arresting the cell cycle at G2/M phase. Finally, the present study demonstrated that overexpression of miR218 could lead to a significant increase in phosphatase and tensin homolog (PTEN) and YY1 transcription factor (YY1), and a decrease in Bcell lymphoma 2 (BCL2) and BMI1 protooncogene, polycomb ring finger (BMI1) at the mRNA and protein level in XWLC05 and NCIH157 cell lines. However, we did not observe any remarkable difference in the roles of miR218 and miR218mediated regulation of BCL2, BMI1, PTEN and YY1 expression in the progression of Xuanwei lung cancer. In conclusion, miR218 could simultaneously suppress cell proliferation and tumor invasiveness and induce cell apoptosis by increasing PTEN and YY1 expression, while decreasing BCL2 and BMI1 in Xuanwei lung cancer. The results demonstrated that miR218 might serve a vital role in tumorigenesis and progression of Xuanwei lung cancer and overexpression of miR218 may be a novel approach for the treatment of Xuanwei lung cancer.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Regulação para Baixo , Neoplasias Pulmonares/genética , MicroRNAs/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sobrevivência Celular , China , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Complexo Repressor Polycomb 1/genética , Complexo Repressor Polycomb 1/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fator de Transcrição YY1/genética , Fator de Transcrição YY1/metabolismoRESUMO
To explore the inhibitive effect of artemether on glioma growth and angiogenesis in brain tumor bearing SD rat. MTT assay was used to evaluate the inhibitory effect of artemether treatment on C6 glioma cells. Forty SD rats which were subcutaneous planted with SD rat C6 glioma cell to establish SD rat orthotopic glioma model were divided resourcefully into 5 groups. each group was 8 rats. Length-path (a mm) and short-path (b mm) of tumor each rat was measured. Tumor volume was calculated using the following formula: V (mm(3)) = a(2)bpi/6. Microvessel density (MVD) in different therapy groups was significantly lower than that in normal saline control group and brain glioma volume in different therapy groups was significantly smaller than that in normal saline control group. There were remarkably inhibitory effects of artmeter on brain glioma growth and angiogenesis in SD rats and the mechanism that artemether inhibited brain glioma growth might be penetrating the blood-brain barrier and inhibiting angiogenesis.