Research Progress of Key Molecular Events Related to Progression of Colorectal Cancer / 肿瘤防治研究

The continuous development of high-throughput and single-cell sequencing technologies and the emergence of spatial transcriptome sequencing have allowed the continuous discovery of temporal and spatial molecular events in the progression of colorectal cancer (CRC) to better understand its mechanism of malignant progression. Genetic variations (mutation of APC and P53, etc.) and mismatch repair of DNA, posttranscriptional regulation, such as epigenetic alteration, and dynamic alteration of complex molecular networks have their own special molecules that play key roles. Drug resistance and metastasis in the late stage of CRC progression are closely related to these key molecular events. This article reviews the research progress and explores key molecular events in the malignant progression of CRC to provide scientific basis and ideas for elucidating the regulatory mechanism of CRC and evaluating its prognosis prediction and treatment.

Overexpression of long noncoding RNA HMMR-AS1 promotes progression of lung adenocarcinoma / 临床检验杂志

Objective@#The purpose of this study is to explore the biological function of long non-coding RNA (lncRNA) HMMR-AS1 in proliferation and metastasis of lung adenocarcinoma (LUAD). @*Methods@#Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of HMMR-AS1 and its sense strand HMMR in LUAD cell lines. Then we knock down the HMMR-AS1 expression through small interfering RNA and evaluate the transfection efficiency and its effect on the expression of HMMR. CCK-8 (cell counting kit), clone formation, flow cytometric analysis, wound scratch assay and transwell assay were used to assess the biological function of A549 and H1299 cells. Western blot was used to detect the protein expression of HMMR in the two cell lines after transfection with si-HMMR-AS1. @*Results@#The expression of HMMR-AS1 in A549 and H1299 cells of LUAD cell line was markedly higher than that in normal lung epithelial cell BEAS-2A by upregulating approximately 3.06 and 5.02 folds (P＜0.05), respectively. After transfection with si-HMMR-AS1, the expression of HMMR-AS1 markedly reduced in both levels of transcription and protein (P＜0.05). Furthermore, knocking down of HMMR-AS1 significantly inhibited the proliferation, migration and invasion abilities, and increased the apoptosis rates of A549 and H1299 cells. @*Conclusion@#LncRNA HMMR-AS1 could promote malignant progression of LUAD cells through enhancing the growth, migration and invasion ability of LUAD cells.

High expression of DNMT3B promotes proliferation and invasion of hepatocellular carcinoma cells Hippo signaling pathway / 南方医科大学学报

OBJECTIVE@#To explore the role of DNMT3B in regulating the proliferation and invasion of hepatocellular carcinoma (HCC) cells.@*METHODS@#We collected the tumor tissues and adjacent tissues from a total of 175 patients with HCC diagnosed in the Second Affiliated Hospital of Chongqing Medical University between May, 2008 and May, 2013 to prepare the tissue microarrays. The association of the expression of DNMT3B with the prognosis and the tumor-free survival and tumor-specific survival rates of the patients was analyzed. Univariate and multivariate Cox regression analyses were used to analyze the effect of DNMT3B expression on the prognosis of HCC. We used RNA interference technique to knock down the expression of DNMT3B in Huh-7 hepatoma cells and observed the changes in cell proliferation using CCK-8 assay and EDU staining and in cell migration and invasion ability using Transwell assay.@*RESULTS@#The positive rates of DNMT3B was significantly higher in HCC tissues than in paired adjacent tissues (67.4% 41.1%, =0.015). A high DNMT3B expression in HCC was significantly associated with the tumor size (=0.001), vascular invasion (=0.004), and intrahepatic metastasis (=0.018). The patients with high DNMT3B expressions had significantly lower tumor-free and tumor-specific survival rates than those with low DNMT3B expressions ( < 0.005). In Huh-7 cells, silencing DNMT3B significantly inhibited the cell proliferation and inhibited cell migration and invasion. Western blotting showed that silencing DNMT3B obviously increased LATS1 expression, decreased the expression of YAP1, and activated Hippo signaling pathway. Methylation-specific PCR showed that the methylation level of LATS1 was decreased in the cells with DNMT3B silencing.@*CONCLUSIONS@#The expression level of DNMT3B is significantly higher HCC tissues than in the adjacent tissues, and the high expression of DNMT3B is closely related to the low survival rate of the patients. Silencing DNMT3B inhibits the proliferation, migration and invasion of HCC cells. DNMT3B promotes the progression of HCC primarily by enhancing the expression of YAP1 through methylation of LATS1 and inhibition of its expression, which inhibits the anti-cancer effect of Hippo signaling pathway.

Sirtuins in malignant progression of tumor / 药学学报

As a post-translational modification, protein acetylation plays an important role in the regulation of apoptosis, mitochondriopoiesis, lipid metabolism and cellular stress response. The imbalance of acetylation and deacetylation has been blamed for the tumorigenesis and malignant progression, which is gradually considered as a promising therapeutic target. Mammalian sirtuins, a NAD+ dependent class Ⅲ HDACs, are closely related to the development of aging, tumor, diabetes, obesity and neurodegenerative diseases. To provide a theoretical basis for the development of new anti-tumor drugs and the treatment of malignant tumors, this paper is prepared to focus on the irreplaceable role of sirtuins in tumor evolution:maintaining genomic stability, regulating energy metabolism, and facilitating tumor cells stemness. The modulator and pathways of sirtuins family and the research progress of agonists and inhibitors are also reviewed. The functions of SIRT2 in resistance, proliferation and metastasis have been highlighted.

Expression of Epidermal Growth Factor Receptor in Astrocytoma

It has been demonstrated that the epidermal growth factor receptor(EGFR) gene, the normal human counterpart of the viral erb-B oncogene, is amplified and overexpressed in 40-50% of malignant astrocytomas. Although little is known about the functional status of the overexpressed protein molecule, overexpression of a growth factor receptor evenly distributed throughout a tumor would be an ideal target for monoclonal antibody or growth factor receptor targeted therapy. We undertook the immunohistochemical study of the EGFR with malignancy grade. The results were as follows 1) Expression of EGFR was deteced in 1 case(6.7%) of low grade astrocytoma, 14 cases(63.6%) of anaplastic astrocytoma and 19 cases(73.1%) of glioblastoma multiforme. It was more frequent in malignant astrocytoma that low grade astrocytoma(p<0.01). 2) The distributed proportion and staing density of EGFR-expressed tumor cells was more increased in glioblastoma multiforme than anaplastic astrocytoma. 3) Regional heterogeneity of EGFR-expressed tumor cells was recognized in cases of EGFR expressed malignant astrocytoma. These results suggest that overexpression of EGFR would be involved in malignant progression of astrocytoma, and the use of monoclonal antibody or growth factor receptor targeted therapy maybe limited due to heterogeneity of EGFR expressed tumor cells in malignant asrotcytoma.