ARHGAP9 inhibits colorectal cancer cell proliferation, invasion and EMT via targeting PI3K/AKT/mTOR signaling pathway.

In digestive system, colorectal cancer (CRC) is a common malignant tumor. The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of the rapamycin (PI3K/AKT/mTOR) signaling pathway plays a central role in CRC, and the aberrant activation of this pathway is associated with tumorigenesis. We aimed to explore the role of Rho GTPase activating protein 9 (ARHGAP9) in the progression of CRC as well as its regulatory effects on the PI3K/AKT/mTOR pathway. The expression of ARHGAP9 in CRC tumor tissues and cell lines were detected using reverse transcription-quantitative PCR (qRT-PCR). 5-ethynyl-2'-deoxyuridine (EdU) assay was applied to test the cell proliferation. Cell migration and invasion were both assessed through transwell assay. Xenograft mouse models were constructed to explore the effects of ARHGAP9 on CRC in vivo. The expressions of PI3K/AKT/mTOR-activating factors and epithelial-mesenchymal transition (EMT)-related factors were all determined using western blot. LY294002 was employed to block PI3K/AKT/mTOR pathway in CRC cells. The expression of ARHGAP9 was down-regulated in CRC tumor tissues and cell lines when compared to normal tissues and cells. The over-expression of ARHGAP9 inhibited cell proliferation, invasion, migration and EMT in CRC cell lines while the knockdown of ARHGAP9 promoted them. In addition, ARHGAP9 up-regulation inhibited the activation of PI3K/AKT/mTOR signaling pathway in CRC cell lines while ARHGAP9 down-regulation led to an opposite effect. The over-expression of ARHGAP9 suppressed CRC tumor growth in vivo. When the PI3K/AKT/mTOR pathway was blocked in CRC cells, the effects of ARHGAP9 knockdown on cell proliferation, migration, invasion and EMT were all overturned. ARHGAP9 inhibited the malignant phenotypes of CRC cells via interdicting PI3K/AKT/mTOR signaling pathway.

Sun J ，Zhao X ，Jiang H ，Yang T ，Li D ，Yang X ，Jia A ，Ma Y ，Qian Z ... -  《-》

[LncRNA SNHG11 promotes malignant progression of colorectal cancer cells through the PI3K/Akt/mTOR signaling pathway].

Tao SN ，Liu XC ，Wang YY ，Yang H ... -  《-》

FAT4 regulates the EMT and autophagy in colorectal cancer cells in part via the PI3K-AKT signaling axis.

Wei R ，Xiao Y ，Song Y ，Yuan H ，Luo J ，Xu W ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》

Pyrroline-5-Carboxylate Reductase-2 Promotes Colorectal Cancer Progression via Activating PI3K/AKT/mTOR Pathway.

The aim of this study was to investigate the effect and underlying pathway of pyrroline-5-carboxylate reductase-2 (PYCR2) on colorectal cancer (CRC). The Cancer Genome Atlas (TCGA) database was used to analyze PYCR2 expression levels and clinical information. Cell proliferation was evaluated using colony forming and EdU assay. Cell apoptosis rate was determined using flow cytometry. Cell migration and invasion were measured by performing a Transwell assay, and PYCR2, MMP-2, MMP-9, Bax, cleaved caspase-3, Bcl-2, cleaved PARP, p-PI3K, PI3K, p-AKT, AKT, p-mTOR, and mTOR protein levels were detected by Western blot. A review of the TCGA database revealed that PYCR2 was highly expressed in CRC patients and that high PYCR2 expression was associated with advanced stage, adenocarcinoma, nodal metastasis, and poor survival rate. Moreover, PYCR2 knockdown reduced cell viability, proliferation, migration, and invasion and increased apoptosis. Additionally, PYCR2 knockdown increased Bax, cleaved caspase-3, and cleaved PARP levels and decreased Bcl-2, MMP-2, MMP-9, p-PI3K, p-AKT, and p-mTOR levels in CRC cells. Effects of silencing PYCR2 on proliferation, migration, invasion, apoptosis, and the PI3K/AKT/mTOR pathway in CRC cells were all reversed using a PI3K activator (740Y-P). PYCR2 was highly expressed in CRC, and its knockdown suppressed CRC tumorigenesis via inhibiting the activation of PI3K/AKT/mTOR pathway. This finding provides a new theoretical foundation for the treatment of CRC.

Yin F ，Huang X ，Xuan Y 《-》

The up-regulated lncRNA DLX6-AS1 in colorectal cancer promotes cell proliferation, invasion and migration via modulating PI3K/AKT/mTOR pathway.

Zhang JJ ，Xu WR ，Chen B ，Wang YY ，Yang N ，Wang LJ ，Zhang YL ... -  《-》