Knockdown of GRHL2 inhibited proliferation and induced apoptosis of colorectal cancer by suppressing the PI3K/Akt pathway.

Grainyhead-like 2 (GRHL2) transcription factor is implicated in many types of cancers. However, the role of GRHL2 in colorectal cancer (CRC) has not been fully understood. The present study aimed to evaluate the expression and functional roles of GRHL2 in CRC. The expression of GRHL2 in normal human intestinal epithelial cells and colorectal cancer cells was measured by qRT-PCR and western blot. For knockdown of GRHL2, two small interfere RNAs (siRNAs) targeting GRHL2 or control siRNA was transfected into CRC cell lines (HCT116 and HT29). For GRHL2 overexpression, the GRHL2-overexpressing vector or empty lentiviral vector was infected into HCT116 and HT29 cells. Cell proliferation was measured by MTT assay. Cell apoptosis rate was analyzed by flow cytometry. The expression of proliferating cell nuclear antigen (PCNA), Bax, and Bcl-2 was detected by western blot. We found that GRHL2 was upregulated in CRC cells compared to normal human intestinal epithelial cells. Knockdown of GRHL2 inactivated the PI3K/Akt pathway in HCT116 and HT29 cells. Knockdown of GRHL2 inhibited cell viability, elevated the apoptosis rates, suppressed the expression of PCNA and Bcl-2, and induced the expression of Bax in HCT116 and HT29 cells, and these effects were reversed by activation of the PI3K/Akt pathway. Inhibition of PI3K/Akt pathway blocked the effects of GRHL2 overexpression on cell proliferation and apoptosis. In conclusion, GRHL2 acted as an oncoprotein through regulating cell proliferation and apoptosis in CRC cells. The PI3K/Akt pathway was closely involved in the effects of GRHL2. Therefore, GRHL2 might be a therapeutic target for the CRC treatment.

Hu F ，He Z ，Sun C ，Rong D ... -  《-》

GRHL2 inhibits colorectal cancer progression and metastasis via oppressing epithelial-mesenchymal transition.

Yang Z ，Wu D ，Chen Y ，Min Z ，Quan Y ... -  《-》

Long noncoding RNA SNHG14 accelerates cell proliferation, migration, invasion and suppresses apoptosis in colorectal cancer cells by targeting miR-944/KRAS axis through PI3K/AKT pathway.

Pei Q ，Liu GS ，Li HP ，Zhang Y ，Xu XC ，Gao H ，Zhang W ，Li T ... -  《-》

Effects of Glut1 gene silencing on proliferation, differentiation, and apoptosis of colorectal cancer cells by targeting the TGF-β/PI3K-AKT-mTOR signaling pathway.

This study aims to investigate the effects of glucose transport l (Glut1) gene on proliferation, differentiation, and apoptosis of colorectal cancer (CRC) cells by regulating the TGF-β/PI3K-AKT-mTOR signaling pathway. Immunohistochemistry was conducted to detect the positive Glut1 expression. Normal human CRC epithelial cells (CCD-18Co) and CRC cell line HCT116 were grouped into the control, blank, negative control (NC), and shGlut1-1 groups. RT-qPCR and Western blotting were performed to detect the expressions of Glut1, TGF-β1, PI3K, AKT, PTEN, mTOR, Bcl-2, and Bax. Protein expression of phosphorylated-PI3K (p-PI3K), p-S473-AKT, p-S389-S6K1, p-T70-4EBP1, Cleaved caspase-3 and Cleaved-PARP were detected. MTT assay, flow cytometry, and colony formation assay were performed in order to detect cell viability, cell cycle, and apoptosis, respectively. The positive expression rate of Glut1 in CRC tissues was 75% ± 8%, while in the adjacent normal tissues it was 0%. In comparison to adjacent normal tissues, CRC tissues had increased Glut1, TGF-β1, PI3K, AKT, mTOR, and Bcl-2 expressions, and p-PI3K, p-S473-AKT, p-S389-S6K1, and p-T70-4EBP1 expressions; and decreased PTEN, Bax, Cleaved caspase-3, and Cleaved-PARP expressions. In comparison with the blank and NC groups, cells in the shGlut1-1 group showed decreased Glut1, TGF-β1, PI3K, AKT, mTOR, and Bcl-2 expressions, and p-PI3K, p-S473-AKT, p-S389-S6K1, and p-T70-4EBP1 expressions; and increased PTEN, Bax, Cleaved caspase-3, and Cleaved-PARP expressions, along with more arrested cells in C0/C1 phase than in S phase and slower cell growth. These results suggested that silencing the Glut1 gene inhibited proliferation and promoted apoptosis of CRC cells by inactivating TGF-β/PI3K-AKT-mTOR signaling pathway.

Wu XL ，Wang LK ，Yang DD ，Qu M ，Yang YJ ，Guo F ，Han L ，Xue J ... -  《-》

Downregulation of GRHL2 inhibits the proliferation of colorectal cancer cells by targeting ZEB1.

Quan Y ，Jin R ，Huang A ，Zhao H ，Feng B ，Zang L ，Zheng M ... -  《-》