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Circadian gene hClock enhances proliferation and inhibits apoptosis of human colorectal carcinoma cells in vitro and in vivo.

ABSTRACT: Colorectal carcinoma (CRC) is one of the most prevalent types of malignancy?associated mortality worldwide. Previous studies have demonstrated that amplification and overexpression of the human circadian locomotor output cycles kaput gene (hClock) was closely associated with a high risk for CRC as well as poor prognosis in CRC patients. However, the underlying molecular mechanisms of CRC remain to be fully elucidated. In the present study, hClock was exogenously overexpressed in the CRC cell line SW480 via infection of a lentivirus vector expressing hClock; in addition, a lentivirus vector?based RNA interference approach, using short hairpin RNA, was performed in order to knockdown hClock in SW620 cells. The results showed that upregulation of hClock promoted proliferation and inhibited apoptosis in SW480 cells in vitro and in vivo, while downregulation of hClock inhibited SW620 cell proliferation and accelerated apoptosis in vitro. Upregulation of hClock enhanced the activity of the anti?apoptotic gene phosphorpylated (p?)AKT and inhibited the expression of the pro?apoptotic gene B cell lymphoma?2 (Bcl?2)?associated X protein and Bcl?2 homology 3 interacting domain death agonist. Furthermore, targeted inhibition of hClock activity reduced p?AKT expression. In conclusion, the results of the present study suggested that the circadian gene hClock promoted CRC progression and inhibit tumor cell apoptosis in vitro and in vivo, while silencing hClock was able to reverse this effect.

SUBMITTER: Wang Y

PROVIDER: S-EPMC4394946 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Circadian gene hClock enhances proliferation and inhibits apoptosis of human colorectal carcinoma cells in vitro and in vivo.

Wang Yaping Y Qian Ruizhe R Sun Ning N Lu Chao C Chen Zongyou Z Hua Luchun L

Molecular medicine reports 20150126 6

Colorectal carcinoma (CRC) is one of the most prevalent types of malignancy‑associated mortality worldwide. Previous studies have demonstrated that amplification and overexpression of the human circadian locomotor output cycles kaput gene (hClock) was closely associated with a high risk for CRC as well as poor prognosis in CRC patients. However, the underlying molecular mechanisms of CRC remain to be fully elucidated. In the present study, hClock was exogenously overexpressed in the CRC cell lin ...[more]

PMID: 25625359

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Circadian gene hClock enhances proliferation and inhibits apoptosis of human colorectal carcinoma cells in vitro and in vivo.

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Circadian gene hClock enhances proliferation and inhibits apoptosis of human colorectal carcinoma cells in vitro and in vivo.

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