Potent antitumor efficacy of ST13 for colorectal cancer mediated by oncolytic adenovirus via mitochondrial apoptotic cell death.

ST13 is a cofactor of heat shock protein 70 (Hsp70). To date, all data since the discovery of ST13 in 1993 until more recent studies in 2007 have proved that ST13 is downregulated in tumors and it was proposed to be a tumor suppressor gene, but no work reported its antitumor effect and apoptotic mechanism. In the work described in this paper, ST13 was inserted into ZD55, an oncolytic adenovirus with the E1B 55-kDa gene deleted, to form ZD55-ST13, which exerts an excellent antitumor effect in vitro and in an animal model of colorectal carcinoma SW620 xenograft. ZD55-ST13 inhibited tumor cells 100-fold more than Ad-ST13 and ZD55-EGFP in vitro. However, ZD55-ST13 showed no damage of normal fibroblast MRC5 cells. In exploring the mechanism of ZD55-ST13 in tumor cell killing, we found that ZD55-ST13-infected SW620 cells formed apoptotic bodies and presented obvious apoptosis phenomena. ZD55-ST13 induced the upregulation of Hsp70, the downregulation of antiapoptotic gene Bcl-2, and the release of cytochrome c. Cytochrome c triggered apoptosis by activating caspase-9 and caspase-3, which cleave the enzyme poly(ADP-ribose) polymerase in ZD55-ST13-infected SW620 cells. In summary, overexpressed ST13 as mediated by oncolytic adenovirus could exert potent antitumor activity via the intrinsic apoptotic pathway and has the potential to become a novel therapeutic for colorectal cancer gene therapy.

[The genetic effects of IGF2 gene intron3 variance in pigs].

A mispairing PCR-RFLP technique was applied in this study to determine the Insulin-like Growth Factor 2(IGF2) gene intron3 G3072A mutation in an outbred Landrace and Large White, and the gelded boars from Landrace x Large White cross. The difference of corresponding traits and the genetic effects of the boars inherited from parental A allele and inherited from parental G allele were analyzed. The results indicated that comparing with the boars inherited from parental G allele, the boars inherited from parental A allele increased significantly in the circumference 3.06% (P< 0.05) and index of body 3.01% (P< 0.05), respectively. The boars inherited from parental A allele had a significantly less average buttock fat thickness (15.31%, P< 0.01), thorax-waist fat thickness (23.74%, P< 0.01), skin thickness 9.38% (P< 0.01), fiber density (20.03%, P< 0.01) and had more less 6th-7th rib fat thickness (20.27%, P< 0.05), tendernce (17.32%, P< 0.05), and had more thick shoulder fat thickness (7.97%, P< 0.05), and had bigger the loin eye area (22.58%, P< 0.01) and fiber cross-sectional area (32.70%, P< 0.01) and fiber diameter (15.38%, P< 0.01) and lean meat (2.18%, P< 0.01) than the boars inherited from parental G allele. The results were suggested that the parental A allele has highly significant genetic effects in improving pig body development and carcass lean percent by increasing fiber diameter and the loin eye area, and decreasing the skin thickness and fat percent.

miR-26b promotes granulosa cell apoptosis by targeting ATM during follicular atresia in porcine ovary.

More than 99% of ovarian follicles undergo atresia in mammals, but the mechanism of follicular atresia remains to be elucidated. In this study, we explored microRNA (miRNA) regulation of follicular atresia in porcine ovary. A miRNA expression profile was constructed for healthy, early atretic, and progressively atretic follicles, and the differentially expressed miRNAs were selected and analyzed. We found that miR-26b, which was upregulated during follicular atresia, increased the number of DNA breaks and promoted granulosa cell apoptosis by targeting the ataxia telangiectasia mutated gene directly in vitro.