LncRNA SNHG7 promotes the proliferation of esophageal cancer cells and inhibits its apoptosis.

OBJECTIVE: Our research studied the expression of long noncoding RNA (lncRNA) SNHG7 in esophageal cancer cells and tissues. The effect of lncRNA SNHG7 on proliferation and apoptosis of esophageal cancer cells has been discussed. PATIENTS AND METHODS: Si-SNHG7 was transfected into esophageal cancer cells, and qRT-PCR was performed to detect the expression of lncRNA SNHG7 in esophageal cancer cells and tissues. The effect of SNHG7 on the proliferation of esophageal cancer cells was measured by CCK8 assay and plate cloning assay, respectively. Flow cytometry was used to detect the effect of SNHG7 on the cell cycle and apoptosis rate of esophageal cancer cells. Changes in expression of downstream protein p15 and p16 after si-SNHG7 intervention were analyzed by qRT-PCR and Western blot. RESULTS: QRT-PCR showed that the expression of SNHG7 in esophageal cancer tissues and cells was significantly up-regulated. After the si-SNHG7 intervention, the proliferation of esophageal cancer cells was inhibited, the apoptosis rate increased, and the cell cycle was blocked in G1-G0 phase. QRT-PCR and Western blot showed that, after the si-SNHG7 intervention, the expression of p15 and p16 increased significantly. CONCLUSIONS: The expression of SNHG7 in the tissues and cells of esophageal cancer is significantly up-regulated. SNHG7 can partly promote the development of esophageal cancer by regulating the expression of p15 and p16.

Long non-coding RNA DUXAP8 regulates proliferation and invasion of esophageal squamous cell cancer.

OBJECTIVE: The purpose of this research was to detect the expression of long non-coding RNA DUXAP8 in esophageal cancer, and to explore its underlying mechanism in the development of esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: We collected 78 pairs of esophageal cancer tissues and normal adjacent tissues. The mRNA level of DUXAP8 in these esophageal cancer tissues and corresponding adjacent tissues was detected by quantitative Real-time polymerase chain reaction (qRT-PCR). The relationship between DUXAP8 expression and the prognosis of esophageal cancer was analyzed. Small interfering RNA (siRNA) was applied to reduce the expression of DUXAP8 in ESCC cell lines (TE-1 and KYSE520). Meanwhile, the specific effect of DUXAP8 on the biological functions of ESCC cells was analyzed by CCK-8 assay (cell counting kit-8), colony formation assay and transwell assay, respectively. Furthermore, the regulatory effect of DUXAP8 on Wnt/ß-catenin pathway was detected by Western blot. RESULTS: DUXAP8 was overexpressed in ESCC tissues than that of normal adjacent tissues. DUXAP8 expression was positively correlated to tumor stage and lymph node metastasis, whereas negatively correlated to the survival rate of ESCC patients. Cell proliferation, colony formation and invasion abilities were significantly decreased after knockdown of DUXAP8 in ESCC cells. Western blot results showed that DUXAP8 could regulate the occurrence of ESCC via Wnt/ß-catenin pathway. CONCLUSIONS: DUXAP8 expression was significantly correlated with tumor stage, lymph node metastasis and poor prognosis of ESCC patients. DUXAP8 may promote the occurrence of ESCC via Wnt/ß-catenin pathway.

Association between the c.1564A>T genetic polymorphism of the MDR1 gene and hepatocellular carcinoma in Chinese population.

The objective of this study was to evaluate the influence of c.1564A>T genetic polymorphisms in the multidrug resistance 1 gene (MDR1) on hepatocellular carcinoma (HCC) susceptibility through association analysis. A total of 632 HCC patients and 645 cancer-free controls were enrolled in this study. The c.1564A>T genetic polymorphisms were genotyped by created restriction site-polymerase chain reaction (CRS-PCR) and confirmed using DNA sequencing methods. The potential associations of c.1564A>T genetic polymorphisms with the risk of HCC were analyzed by different genetic models. Statistically significantly increased risks of HCC were detected in the homozygote comparison (TT versus AA: OR = 1.70, 95%CI = 1.17-2.45, χ(2) = 7.99, P = 0.005), recessive model (TT versus AT/AA: OR = 1.64, 95%CI = 1.15-2.33, χ(2) = 7.66, P = 0.006), and allele contrast (T versus A: OR = 1.23, 95%CI = 1.04-1.45, χ(2) = 6.09, P = 0.014). Our data suggest that the genotypes/alleles from c.1564A>T genetic polymorphisms are statistically associated with HCC risk. The allele-T and genotype TT may contribute to susceptibility to HCC in the Chinese Han population.

Preassembled capsids of type D retroviruses contain a signal sufficient for targeting specifically to the plasma membrane.

The capsids of Mason-Pfizer monkey virus (M-PMV), an immunosuppressive type D retrovirus, are preassembled in the infected cell cytoplasm and are then transported to the plasma membrane, where they are enveloped in a virus glycoprotein-containing lipid bilayer. The role of viral glycoprotein in intracellular transport of M-PMV capsids was investigated with a spontaneous mutant (5A) of M-PMV, which we show here to be defective in envelope glycoprotein biosynthesis. DNA sequence analysis of the env gene of mutant 5A reveals a single nucleotide deletion in the middle of the gene, which results in the synthesis of a truncated form of the envelope glycoprotein. Evidence is presented showing that the mutant glycoprotein is not expressed at the cell surface but is retained in the endoplasmic reticulum. Normal levels of gag-pro-pol precursor polyproteins are made and processed in mutant genome-transfected cells, and high levels of noninfectious particles lacking viral glycoprotein are released with normal kinetics into the culture medium. No intracisternal budding of capsids is observed. We conclude that viral glycoprotein is required neither for targeting preassembled capsids of M-PMV to the plasma membrane for final maturation nor for the budding process. Since the presence or absence of M-PMV glycoprotein at the site of budding does not affect the efficiency or kinetics of the targeting process, the preassembled capsid of M-PMV, in contrast to those of intracisternal type A particles, appears to have an intrinsic signal for intracellular transport to the plasma membrane.

The env protein of an infectious noncytopathic HIV-2 is deficient in syncytium formation.

A recent isolate of human immunodeficiency virus type 2 (HIV-2) designated HIV-2ST is deficient in its ability to cause the typical cytopathic effects of HIV infection. The pathogenic potential of HIV-2 in inducing human disease may be less than that of HIV-1, and it is of particular interest to establish the basis for the reduced cytopathogenicity of this isolate in vitro. Utilizing recombinant vaccinia viruses (rVV) carrying the envelope genes (env) of HIV-2ST or those of fully cytopathic HIV-1 or HIV-2 isolates, we have investigated envelope glycoprotein expression, processing, transport, and biological function. Radioimmunoprecipitation and polyacrylamide gel electrophoresis (RIP-PAGE) of rVV-infected cell lysates indicated that the proteins expressed by each recombinant were synthesized, processed, and recognized by specific antisera. Immunofluorescence studies showed that the recombinant env gene products of HIV-2ST and HIV-2ROD reach the cell surface and are retained there in similar amounts. Whereas cells expressing the HIV-1 or HIV-2ROD env gene products were found to undergo fusion with uninfected CD4+ cells, no syncytium formation was observed with three CD4+ cell lines exposed to the cells expressing the envelope glycoproteins of HIV-2ST on their surfaces; one CD4+ lymphoid cell line (SupT1) exhibited few very small syncytia in the presence of recombinant HIV-2ST envelope glycoproteins. The failure of the HIV-2ST envelope glycoprotein to induce cell fusion was not the result of an inhibition by cell-associated CD4, since fusion was also not observed when rVVST-infected CD4- cells were cocultured with CD4+ cells. Thus, the HIV-2ST envelope protein itself is defective in its ability to induce cell fusion. Furthermore, the expression, processing, transport, and surface stability of env products of HIV-2ST are unlikely to be responsible for its attenuation, suggesting that the molecular interactions between its env products and target cell membranes are significantly altered.

Molecular characterization of an attenuated human immunodeficiency virus type 2 isolate.

Naturally occurring strains of human immunodeficiency virus (HIV) can vary considerably in their in vitro biological properties, and such differences may also be reflected in their in vivo pathogenesis. In an attempt to define genetic determinants of viral pathogenicity, we have molecularly cloned, sequenced, and characterized an attenuated isolate of HIV type 2 (HIV-2/ST) that differs from prototype HIV-2 strains in its inability to fuse with and kill susceptible CD4-bearing target cells. A proviral clone, termed JSP4-27, was identified to be transfection competent and to fully exhibit the noncytopathic and nonfusogenic properties of its parental isolate. Nucleotide sequence analysis of this clone revealed a genomic organization very similar to that of cytopathic HIV-2 strains and an overall nucleotide sequence homology of 88 to 90%. Amino acid sequence comparison confirmed the integrity of all major viral gene products in JSP4-27 but identified two amino acid sequence substitutions in its envelope fusion region. To investigate whether these mutations were responsible for the nonfusogenic phenotype of JSP4-27, we amplified, cloned, and sequenced the envelope fusion regions of four additional HIV-2/ST strains, two of which represented in vitro-generated, fusogenic and cytopathic variants of HIV-2/ST. The analysis showed that all HIV-2/ST strains examined, including the fusogenic variants, contained the same amino acid sequence changes. On the basis of these findings, we conclude that the attenuated phenotype of JSP4-27, and that of its parental virus, is not due to a direct alteration of the envelope fusion domain. Our results also show, for the first time, that individual replication-competent proviral clones can be representative of attenuated strains of HIV.