KLF14 targets ITGB1 to inhibit the progression of cervical cancer via the PI3K/AKT signalling pathway

Abstract

Our study aimed to determine whether Krüppel-like factor 14 (KLF14) inhibits the proliferation and promotes the apoptosis of cervical cancer cells through integrin β1 (ITGB1). Immunohistochemistry was performed to determine the expression of KLF14. The effect of KLF14 on the proliferation of cervical cancer cells was verified by Cell Counting Kit-8 (CCK-8) assays, colony formation assays and in vivo experiments. The effect of KLF14 on cervical cancer cell apoptosis was detected by flow cytometry. The targeting relationship between KLF14 and ITGB1 was evaluated by Western blotting and a dual-luciferase reporter assay. Moreover, Flow cytometry was performed to verify the relationship between KLF14 and ITGB1 on the apoptosis of cervical cancer cells. Additionally, Western blot analysis was performed to investigate the relationship between KLF14 and ITGB1 on the expression of downstream related molecules. As a result, the expression of KLF14 in cervical cancer tissues was lower than that in paracancerous tissues. KLF14 inhibited proliferation and promoted apoptosis in cervical cancer cells. Mechanistically, ITGB1 expression was significantly downregulated in KLF14-overexpressing cervical cancer cells. At the same time, we found that the effects of KLF14 and ITGB1 on apoptosis of cervical cancer cells could be mutually affected. KLF14 directly targeted ITGB1 to regulate its downstream PI3K/AKT signalling pathway. In summary, KLF14 inhibits the progression of cervical cancer by targeting ITGB1 via the PI3K/AKT signalling pathway.

Identification of Itgb1 as a critical gene for radiation-induced injury by bioinformatic analysis combined with experimental verification

“…In previous studies, Itgb1 was highly expressed in glioma, osteosarcoma, and bone marrow mesenchymal stem cells.Itgb1 is a member of the ITG family [21,22], which is closely associated with apoptosis. Itgb1 enhances the radiation resistance of non-small cell lung cancer cells by regulating the DNA damage response [23]and YAP1-induced epithelial-mesenchymal transition [24,25].…”

Circular RNAs and cervical cancer: friends or foes? A landscape on circRNA-mediated regulation of key signaling pathways involved in the onset and progression of HPV-related cervical neoplasms

“…Indeed, as a member of the integrin family, ITGB1 connects the extracellular matrix (ECM) to the intracellular tyrosine kinase PI3K, leading to the activation of PI3K/Akt signaling [ 140 ]. Then, ITGB1-induced over-activation of PI3K/Akt signaling causes an uncontrolled cell proliferation [ 141 ]. Further investigations conducted by the same team revealed that ITGB1 expression was regulated by miR-361-3p in CC cells, in a reverse manner, indicating that miR-361-3p could bind to the ITGB1 to suppress its function for further reduction of cell proliferation and invasion.…”

Krüppel-like factors in tumors: Key regulators and therapeutic avenues

“…KLF14 activates this signaling by enhancing the activation of AKT kinase and preventing AKT phosphorylation ( 38 ). Nevertheless, KLF14 simultaneously suppresses cervical cancer progression by inhibiting integrin beta 1 transcription, which upregulates key molecules in the PI3K/AKT signaling, including AKT and p-AKT, representing an indirect inhibitory effect of KLF14 on PI3K/AKT ( 39 ). The interaction between KLF14 and PI3K is also bidirectional.…”