X-ray repair cross-complementing group 1 Arg399Gln gene polymorphism and susceptibility to colorectal cancer:a meta-analysis.

X-ray repair cross-complementing group 1 (XRCC1), a DNA repair enzyme, plays a crucial role in the base excision repair by generating a single nucleotide repair patch. It has been demonstrated that the XRCC1 Arg399Gln gene polymorphism was associated with variations in XRCC1 enzyme activity. The aim of this study was to quantitatively summarize the association between the XRCC1 Arg399Gln polymorphism and susceptibility to colorectal cancer (CRC). A comprehensive search of the PubMed, Embase, and China National Knowledge Infrastructure databases was conducted for studies on the association between the XRCC1 Arg399Gln polymorphism and CRC risk. Summary odds ratio (OR) with its corresponding 95 % confidence interval (95 %CI) was estimated, in a fixed-effects model or a random-effects model when appropriate, to assess the association. Totally, 26 case-control studies with 6,979 cases and 11,470 controls were included into this meta-analysis. The pooled results of total studies showed that the XRCC1 Arg399Gln polymorphism was significantly associated with increased risk of CRC in all genetic contrast models (OR(A vs. G) = 1.13, 95 %CI 1.03-1.23, P (OR) = 0.008; OR(Gln/Gln vs. Arg/Arg) = 1.24, 95 %CI 1.04-1.46, P (OR) = 0.015; OR(Gln/Gln vs. Arg/Gln + Arg/Arg) = 1.19, 95 %CI 1.03-1.38, P (OR) = 0.021; OR(Gln/Gln + Arg/Gln vs. Arg/Arg) = 1.14, 95 %CI 1.02-1.28, P (OR) = 0.022), except for the additive contrast model (OR(Arg/Gln vs. Arg/Arg) = 1.11, 95 %CI 0.99-1.25, P (OR) = 0.064). The statistically significant association between the XRCC1 Arg399Gln polymorphism and CRC risk was observed among studies with high quality and in Asians, but not in Caucasians. Sensitivity analyses by sequential omission of any individual studies further identified the significant association. Publication bias was inexistent in this meta-analysis. The meta-analysis suggests that the XRCC1 Arg399Gln polymorphism is associated with increased risk of CRC.

LncRNA DLGAP1-AS2 promotes the radioresistance of rectal cancer stem cells by upregulating CD151 expression via E2F1.

BACKGROUND: Radiotherapy resistance is one of the major causes of rectal cancer treatment failure. LncRNA DLGAP1-AS2 participates in the progression of several cancers. We explored the role and potential mechanism of DLGAP1-AS2 in the radioresistance of rectal cancer stem cells. METHODS: HR8348-R cells, radioresistant cells from HR8348 after irradiation, were isolated into CD133 negative (CD133-) and positive (CD133+) cells. Cell proliferation, apoptosis, migration and tumorsphere formation were determined by CCK-8, flow cytometry, wound healing assay and tumorsphere formation assay, respectively. CD133, tumor stem cell drug resistance gene (MDR1 and BCRP1), DNA repair marker (γ-H2AX) and AKT/mTOR/cyclinD1 signaling were measured by Western blot. The relationship between DLGAP1-AS2 and E2F1 was verified using RIP. The interaction between E2F1 and CD151 promoter was confirmed using dual-luciferase reporter gene assay and ChIP. AKT inhibitor API-2 was employed for validating the effect of AKT/mTOR/cyclinD1 signaling in the radioresistance of rectal cancer cells. RESULTS: The DLGAP1-AS2 level was increased in CD133+ cells after irradiation. DLGAP1-AS2 knockdown inhibited the proliferation, migration and tumorsphere formation while stimulating apoptosis in CD133+ cells. DLGAP1-AS2 inhibition downregulated the expression of CD133, MDR1, BCRP1 and γ-H2AX and suppressed AKT/mTOR/cyclinD1 activation. DLGAP1-AS2 upregulated the expression of CD151 by interacting with E2F1. API-2 neutralized the promotive effects of overexpressed CD151 on radioresistance. CONCLUSION: DLGAP1-AS2 accelerates the radioresistance of rectal cancer cells through interactions with E2F1 to upregulate CD151 expression via the activation of the AKT/mTOR/cyclinD1 pathway.

Increased miR-323a induces bladder cancer cell apoptosis by suppressing c-Met.

The current study aimed to evaluate the expression and role of miR-323a in the progression of bladder cancer (BC), thereby providing a theoretical basis and potential therapy methods for BC patients. Our data showed that miR-323a levels were significantly reduced in BC tissues compared with those of non-cancerous tissues. Meanwhile, miR-323a was significantly decreased in human BC cell lines (T24, J82, TCCSUP, RT-112) than that in human normal bladder epithelial cell line SV-HUC-1. Furthermore, inhibition of miR-323a markedly enhanced the migration and invasive capacity of T24 and TCCSUP cells. Moreover, overexpression of miR-323a significantly prompted the apoptosis of BC cells. Dual luciferase reporter assay and western blot analysis confirmed that c-Met was a target gene of miR-323a. More importantly, upregulation of c-Met significantly prompted BC cell proliferation mainly as a result of the enhanced level of phosphorylation of AKT. This effect could be abolished when c-Met was silenced in BC cells. In summary, reduced miR-323a expression in BC contributed to enhanced BC cell proliferation and migration mainly by targeting c-Met.

[Effects of 2A-1-1 on the aggregation and Ca2+ influx of platelets].

OBJECTIVE: To explore the effects of 2A-1-1 (purified component from Panax notoginsengs saponins) on the aggregation of and Ca2+ influx into human platelets. METHODS: The aggregation of platelets was tested by nephelometry, Fura-2 fluorescent technique was used for detecting cell [Ca2+]i. The effects of 2A-1-1, nifedipine and SK&F96365 on Ca(2+) influx into human platelets induced by ADP or CPA were observed separately. RESULTS: Nifedipine (< 20 micromol/L) could not inhibit platelet aggregation induced by ADP or the Ca(2+) influx induced by ADP or CPA. SK&F96365 at 20 micromol/L could inhibit the maximal aggregation of platelets induced by ADP with a inhibitory rate of 59.83%, at 15 micromol/L could inhibit the Ca2+ influx induced by CPA or ADP. 2A-1-1 (5, 10 and 20 micromol/L) could inhibit the maximal aggregation of platelets induced by ADP with the inhibitory rates of 47.06%, 53.47% and 71.52%, respectively. 2A-1-1 at 10 and 20 micromol/L could inhibit the Ca2+ influx induced by CPA or ADP. CONCLUSIONS: 2A-1-1 can inhibit platelets aggregation, block the ROC (Receptor-dependent Ca2+ channels) and inhibit Ca2+ influx of human platelets.