Overexpression of MCPH1 inhibits the migration and invasion of lung cancer cells

Abstract

BackgroundThe role of dysfunction of MCPH1, a recently identified tumor suppressor gene, has not yet been established in lung cancer. In our previous study, it was reported that MCPH1 expression is downregulated in lung cancer tissues and that MCPH1 overexpression inhibits the proliferation of non-small-cell lung cancer cells. The results can be found in the APJC and Oncology Letters journals.MethodsKaplan-Meier survival analysis was conducted to explore the prognostic significance of MCPH1. Cell experiments were performed to investigate the effects of MCPH1 on the biologic behaviors of lung cancer cells.ResultsIn the current study, microarray analysis of MCPH1 revealed that lung cancer patients with high MCPH1 expression had longer relapse-free survival. Overexpression of MCPH1 in A549 lung carcinoma cells successfully inhibited cell migration and invasion. Moreover, overexpression of MCPH1 inhibited migration and invasion by regulating the activities of several proteins that control the epithelial–mesenchymal transition, such as Slug, Snail, E-cadherin, Mdm2, and p53.ConclusionOur results indicate that downregulation of MCPH1 correlates with tumor progression in lung cancer, and hence MCPH1 may be an important tumor suppressor gene and a novel candidate therapeutic target in lung cancer.

The Yin and Yang of Autosomal Recessive Primary Microcephaly Genes: Insights from Neurogenesis and Carcinogenesis

“…Premature neurogenic production [16] Cell cycle and apoptosis (cervical cancer) [40] Reductions in head circumference, premature chromosome condensation, and hypoplasia of the corpus callosum [15] Migration and invasion (lung cancer) [42] MCPH2 (WDR62)…”

“…MCPH1 (BRIT1) CHK1, CDC25, CDK1 [16] SLUG, CDK1, p53, CDH1, MDM2, SNAIL [42] p53 [110] CyclinA2, CDK2, CDC25C-cyclinB, CDC2, p53, BCL-2, Bax, Cytochrome c, Caspase-3, PARP-1 [40] MCPH2 (WDR62) JNK [18] N/A AURKA [119] PLK1 [43] MCPH3 (CDK5RAP2) p35 [120] N/A MST1, TAZ (Hippo) [121] MCPH4 (CASC5) BUB1, BUBR, ZWINT-1 [122] BUB1 [52] miR-193b-3p [27] p53 [123] MCPH5 (ASPM) The p53 gene (TP53) is classified as a tumor suppressor gene, and upregulation of its activity led to neural progenitor apoptosis in MCPH gene-deficient mice. Deletion of Mcph5 increases DNA damage and induces postnatal cerebellar progenitor apoptosis that depends on p53 [114].…”

“…NPC death was dramatically reduced in Citk and Trp53 double KO mice [77]. During carcinogenesis, the overexpression of MCPH1 inhibits the migration and invasion of lung cancer cells through the accumulation of p53 [42]. MCPH1 regulates p53 activity and protein stability through blocking MDM2-mediated p53 ubiquitination in breast cancer cells [110].…”

Primary microcephaly with an unstable genome

“…Some MCPH genes function to suppress tumor growth and proliferation. Downregulated MCPH1 has been reported in many malignant tumors, including breast cancer, lung cancer, ovarian cancer, oral squamous cell carcinoma and prostate cancer (Mai et al 2014;Rai et al 2006;Venkatesh et al 2013;Wu et al 2018). MFSD2A is a novel lung cancer tumor suppressor gene that upon downregulation, leads to the G1 arrest in non-small cell lung cancer cell lines and primary lung adenocarcinomas (Spinola et al 2010).…”

“…CSCs with a tumor initiating potential actively employ several signal cascades including the Wnt pathway, the Sonic hedgehog (shh) pathway, the Hippo pathway and the Notch pathway, which are utilized by several MCPH genes as well. Through Wnt signal pathway, ASPM augments Wnt-Dvl-3-β-catenin Increased cellular proliferation, and increased metastasis associated with highly expression of MCPH1 in breast cancer cells (Venkatesh et al 2013;Tervasmäki et al 2019;Rai et al 2006) Decreased expression cervical cancer cells Promote the migration and invasion of the cancer (Mai et al 2014) Decreased expression non-small cell lung cancer cells Promote the migration and invasion of the cancer (Wu et al 2018) Markedly decreased in ovarian cancer, oral squamous cell carcinoma and prostate cancer cells…”