RAPTOR promotes colorectal cancer proliferation by inducing mTORC1 and upregulating ribosome assembly factor URB1

Abstract

Mammalian target of rapamycin complex 1 (mTORC1) is evolutionally conserved and frequently activated in various tumors, including colorectal cancer (CRC). It has been reported that the ribosome assembly factor Urb1 acts downstream of mTORC1/raptor signaling and contributes to digestive organ development in zebrafish. Previously, we highlighted that URB1 was overexpressed in CRC. Here, we assessed the mTORC1/regulatory associated protein with mTOR (RAPTOR)‐URB1 axis in CRC tumorigenesis. We found that RAPTOR was overexpressed in CRC tissues and cell lines, was a favorable predictor in patients with CRC, and positively correlated with URB1. Silencing of RAPTOR suppressed CRC cell proliferation and migration and induced cell cycle arrest and apoptosis in vitro and inhibited xenograft growth in vivo. Moreover, ectopic overexpression of RAPTOR exerted an inverse biological phenotype. Knockdown of RAPTOR quenched mTORC1 activity and reduced the expression of URB1 and cyclinA2 (CCNA2). In contrast, overexpression of RAPTOR activated mTORC1 and upregulated URB1 and CCNA2. Furthermore, URB1 and CCNA2 expression were also impeded by rapamycin, which is a specific inhibitor of mTORC1. Thus, RAPTOR promoted CRC proliferation, migration, and cell cycle progression by inducing mTORC1 signaling and transcriptional activation of both URB1 and CCNA2. Taken together, we concluded that RAPTOR has the potential to serve as a novel biomarker and therapeutic target for CRC.

Demethylzeylasteral inhibits cell proliferation and enhances cell chemosensitivity to 5-fluorouracil in Colorectal Cancer cells

“…We believed that these 15 genes were key points in the regulation of the whole PPI network. We found that some genes were related to the proliferation and apoptosis of Colorectal cancer, such as EGFR, CDK2, CCN2 and BCL2L1 [23][24][25][26], and some were related to the prediction of chemotherapy for colorectal cancer, such as EGFR, TYMS [27,28]. Others, such as MMP9 [29], were associated with the metastasis of colorectal cancer.…”

Increased PYCR1 mRNA predicts poor prognosis in kidney adenocarcinoma

“…The ribosome is the place for protein synthesis and known as the “protein factory of cells”. [ 26 ] The ubiquitin-proteasome system has a central role in regulating protein activities as well as cell cycle, gene expression, oxidative stress response, cell survival, cell proliferation, and apoptosis. [ 27 ] The p53, previously described as a tumor suppressor, is now considered to be a key component of the mitochondrial apoptosis pathway under cell stress.…”

Establishment of a Colorectal Cancer-Related MicroRNA-mRNA Regulatory Network by Microarray and Bioinformatics

“…There was decreased CCL21 expression in CRC and the expression of lymphangiogenic genes, including CCL21, was associated with poor prognosis of both primary and liver metastatic CRC (Mumtaz et al, 2009;Vellinga et al, 2017). RAPTOR facilitated proliferation, migration, and cell cycle progression by promoting the Mtorc1 pathway and transcriptional activation of both URB1 and CCNA2, and CCNA2 can act as a novel biomarker via regulating growth and apoptosis of CRC (Gan et al, 2018;Wang et al, 2020). Moreover, inhibiting the expression of HELLS impaired CRC cell proliferation and induced cell cycle arrest (Liu et al, 2019a).…”