Rassf7a promotes spinal cord regeneration and controls spindle orientation in neural progenitor cells.

Spinal cord injury (SCI) can cause long-lasting disability in mammals due to the lack of axonal regrowth together with the inability to reinitiate spinal neurogenesis at the injury site. Deciphering the mechanisms that regulate the proliferation and differentiation of neural progenitor cells is critical for understanding spinal neurogenesis after injury. Compared with mammals, zebrafish show a remarkable capability of spinal cord regeneration. Here, we show that Rassf7a, a member of the Ras-association domain family, promotes spinal cord regeneration after injury. Zebrafish larvae harboring a rassf7a mutation show spinal cord regeneration and spinal neurogenesis defects. Live imaging shows abnormal asymmetric neurogenic divisions and spindle orientation defects in mutant neural progenitor cells. In line with this, the expression of rassf7a is enriched in neural progenitor cells. Subcellular analysis shows that Rassf7a localizes to the centrosome and is essential for cell cycle progression. Our data indicate a role for Rassf7a in modulating spindle orientation and the proliferation of neural progenitor cells after spinal cord injury.

Cell cycle arrest induced by trichoplein depletion is independent of cilia assembly.

Cilia assembly and centriole duplication are closely coordinated with cell cycle progression, and inhibition of cilia disassembly impedes cell cycle progression. The centrosomal protein trichoplein (TCHP) has been shown to promote cell cycle progression in the G1 -S phase by disassembling cilia. In this study, we showed that deletion of TCHP not only prevented the progression to the S phase but also resulted in cell cycle exit and entrance into G0 phase. Surprisingly, we found that loss of TCHP-induced G0 arrest could not be reversed by blocking the assembly of cilia. In cells without IFT20 or CEP164, two genes encoding key factors for ciliogenesis, depletion of TCHP still led to G0 arrest. Mechanistically, we also found that TCHP depletion-induced cell cycle arrest was not mediated through a centrosome surveillance mechanism, but inhibition of Rb or concomitant inhibition of both Rb and p53 signaling pathways was required to reverse the cell cycle phenotype. In conclusion, our study provides new insights into the function of TCHP in cell cycle progression.

Lupeol inhibits growth and migration in two human colorectal cancer cell lines by suppression of Wnt-ß-catenin pathway.

BACKGROUND: Lupeol, a triterpene isolated from various herbal plants, possesses an anti-inflammatory function and has been proposed as a candidate for anticancer agents. The purpose of this research was to investigate the effect of lupeol on the viability, apoptosis, cell-cycle distribution, and migration of colorectal cancer cell lines and its molecular mechanism. METHODS: Lupeol was assessed for its anticancer effect using two human colorectal cancer cell lines: SW480 and HCT116. These cells were treated with lupeol, and their viability, apoptosis, migration, and cycle distribution were detected by CCK8, flow cytometry, and the transwell method. Quantitative PCR, Western blot, and immunofluorescence were applied to detect the expressions of CTNNB1, TCF4, cMYC, CCND1, CLDN1, and CCNA2. RESULTS: Lupeol suppressed cell viability and migration and induced cellular apoptosis of both cell lines, with increased p53 and decreased Bcl2 protein levels (P<0.05). Cell cycles of both lupeol-treated cell lines were arrested in the S phase (P<0.05). Quantitative PCR and Western blot analyses showed significantly reduced expressions of CTNNB1, TCF4, and downstream genes of the Wnt-ß-catenin pathway, including the cell-cycle-regulated genes of cMYC and CCND1 of both cell lines upon lupeol treatment (P<0.05). mRNA and protein levels of CLDN1 decreased in HCT116 cells, plus the expression of CCNA2 mRNA and protein decreased in SW480 cells (P<0.05). Immunofluorescence analysis confirmed decreased expression of Wnt-ß-catenin signaling. CONCLUSION: Our findings indicate that lupeol effectively inhibits proliferation and migration and induces apoptosis and cell-cycle arrest of two colorectal cell lines by inactivation of the Wnt-ß-catenin signaling pathway and downregulation of cMYC, CCND1, CCNA2, and CLDN1, thereby making it a promising anticancer candidate.