Overexpression of MCPH1 inhibits uncontrolled cell growth by promoting cell apoptosis and arresting the cell cycle in S and G2/M phase in lung cancer cells

Abstract

Abstract. Microcephalin (MCPH1/BRIT1) is a large nuclear protein that is involved in the early cellular response to DNA damage, the expression of which is reduced in a variety of types of human tumors. A recent study by our group demonstrated that MCPH1 expression is markedly decreased in lung cancer. However, it remains unclear whether inducing the expression of MCPH1 may ameliorate lung cancer, and, if so, which mechanisms underlie this process. The results of the present study demonstrated that MCPH1 expression was downregulated in lung cancer tissues compared with that in normal lung tissues. Furthermore, MCPH1 overexpression in A549 non-small cell lung carcinoma cells, successfully inhibited cell proliferation via arrest of the cell cycle in the S and G2/M phases. In addition, MCPH1 overexpression promoted cell apoptosis, in association with a significant increase in the quantities of Bax and active caspase-3, as well as a decrease in the level of Bcl-2. In conclusion the present results indicated that MCPH1 is involved in the regulation of apoptosis and entry into mitosis, suggesting that MCPH1 may function as a tumor suppressor and that it may be important in the pathogenesis of lung cancer.

The E3 ubiquitin ligase APC / C C dh1 degrades MCPH 1 after MCPH1‐βTr CP 2‐Cdc25A‐mediated mitotic entry to ensure neurogenesis

“…However, it is unclear how a sustained expression of MCPH1 is toxic to cells. It is interesting to note two recent publications showing that the overexpression of MCPH1 inhibits cell proliferation by promoting apoptosis (Zhou et al , ) and activating the cytochrome c‐caspase 3 signaling (Mai et al , ). The ubiquitination of MCPH1 is realized by a direct interaction of MCPH1 with Cdh1 and also possibly by an interaction with the scaffold component Cdc27 of APC/C (Singh et al , ).…”

Structural characterization of centipede oligopeptides and capability detection in human small cell lung carcinoma: inducing apoptosis

“…The main property of tumor cells is uncontrollable cell growth, and the cell cycle arresting becomes a pivotal therapy target in remedies. 21 The above studies showed that SSMO-5 can induce apoptosis; therefore, the effect of SSMO-5 on the cell cycle was investigated by ow cytometry (Fig. 3).…”

Genetic association and functional characterization of MCPH1 gene variation in bipolar disorder and schizophrenia

“…The MCPH1 gene, also known as BRIT1 , has been shown to be associated with autosomal recessive primary microcephaly (Jackson et al, ). Overexpression of the MCPH1 gene has been reported to inhibit uncontrolled lung cancer cell growth by promoting cell apoptosis and arresting the cell cycle in S and G2/M phase (Zhou et al, ). Here, we have found that overexpression of a clone containing the reference MCPH1 sequence led to a decrease in cell counts.…”