KLF4 overexpression

Finally, rescue experiment demonstrated that using mTORC1 pathway inhibitor could attenuate the cisplatin resistance induced by the overexpression of KLF4. In conclusion, our research indicates that KLF4 promotes cisplatin resistance through the activation of mTORC1 signaling, and proposes that inhibiting KLF4 might serve as a viable therapeutic approach to overcoming drug resistance in ovarian cancer.

Our data revealed a previously unidentified function of KLF14 in promoting ferroptosis, which results in the suppression of cell proliferation. Mechanistically, we revealed a novel regulatory mechanism by which KLF14 targets GPX4. These findings suggest a novel strategy to induce ferroptosis through the targeting of KLF14 in human cervical cancer cells.

In vivo experiments showed that overexpression of LATS2 enhanced the sensitivity of ovarian cancer to DDP. KLF4 activates LATS2 via DNA damage to enhance DDP sensitivity in ovarian cancer, providing a potential target for improving treatment outcomes.

Electrophysiology showed that PTZ-induced action potential frequency was decreased by overexpression of Klf4. In conclusion, these findings suggest that Klf4 plays an important role in regulating PTZ-induced seizures and therefore constitutes a new molecular target that should be explored for the development of antiepileptic drugs.

Furthermore, our findings showed that miR-150-3p was dramatically upregulated under brusatol treatment which resulted in the downregulation of KLF4. Our results suggested that the miR-150-3p/KLF4/NCK2 axis might play an important role in the antitumour effects of brusatol in melanoma.

TNF-α promotes KLF4 expression, while TNF-α promotes apoptosis in SK-BR-3 cells, a process that may be due to elevated KLF4 protein expression.

KLF14 also activated the JNK pathway to induce S-phase arrest and promote the expression of CDK2 and CCNA2. In summary, KLF14 activates the JNK-signaling pathway to induce S-phase arrest in cervical cancer cells.

Finally, we investigated whether pharmacological induction of KLF4 using APTO-253, a small-molecule inducer of KLF4, could control leukemia...Moreover, pharmacological induction of KLF4 demonstrated anti-leukemic activity in T-ALL cells. These findings propose a promising strategy for patients with T-ALL and 5' TAL1 SE.

Accumulating studies demonstrated that resistance of colon cancer (CC) to 5-fluorouracil (5-FU) contributes to adverse prognosis...Autophagy activator Rapamycin or sh-RAB26 treatment reversed the impact of KLF4 overexpression on 5-FU resistance...Rescue experiments revealed that KLF4 targeted RAB26 to inhibit CC cell autophagy, resulting in decreasing the resistance to 5-FU. KLF4 strengthened the sensitivity of CC cells to 5-FU by targeting RAB26 to restrain autophagy pathway.

The cells were confirmed by differentiation assays using dexamethasone and insulin as adipogenesis-inducing agents and also Staurosporine as a neural-inducing agent...However, hsa-miR-4270 mimic had opposite effects on the cell viability and gene expression of the stem cell markers. Effect of hsa-miR-4270 inhibitor and mimic on the expression of the stem cell markers in GCSCs indicated that hsa-miR-4270 stimulates the stemness property of GCSCs, likely through stimulating the development of gastric stem cells.

We also found circ_0020256 accelerated CCA tumor growth in vivo. In conclusion, circ_0020256 promoted fibroblast activation to facilitate CCA progression via EIF4A3/KLF4 pathway, providing a potential intervention for CCA progression.

KLF4 is supposed to play a critical role in DR4/DR5 expression and responses to TRAIL and cisplatin, whereas Nanog is only implicated in the former events only. Direct regulation of death receptor expression and TRAIL response by KLF4 and Nanog have not been well documented previously, and the regulatory mechanism behind the process remains to be elucidated.

KLF14 acts as a tumor suppressor which inhibits the proliferation of HCC cells by modulating cellular iron metabolism via the repression of IRP2. We identified Fluphenazine, as an activator of KLF14, could be a potential compound for HCC therapy. Our findings therefore provide an innovative insight into the pathogenesis of HCC and a promising therapeutic target.

This work strongly suggests that an pEMT-like pathway is activated in recurrent and Cisplatin-resistant HNSCC. Finally, stable KLF4-overexpression might sensitize HNSCC tumor cells for Cisplatin treatment.

In conclusion, KLF4 significantly inhibited the proliferation, invasion and migration of NSCLC cells via inactivation of MSI2/JAK2/STAT3 signalling pathway. Thereby, our finding might shed new lights on exploring the new strategies against NSCLC.

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.

Furthermore, we characterized the dynamic alterations in the Klf4 cis-regulatory network during APL progression and demonstrated that ectopic Klf4 overexpression can suppress self-renewal and reverse the differentiation block induced by PML-RARα. Our study provides a comprehensive in vivo temporal dissection of the epigenomic and topological reprogramming induced by an oncogenic TF and illustrates how topological architecture can be used to identify new drivers of malignant transformation.

The presence of HSP-70 ensures the membranous localization of E-cadherin, therefore, the ability of cells to form cadherin/catenin complexes and cellular linkages. In conclusion, KLF4 is a major regulator of the epithelial cadherin-adhesion in HNSCC.

In addition, KLF4 overexpression significantly increased melanin production and pigment-related gene expression. Collectively, our findings show that KLF4 is important for coat color formation and melanocyte homeostasis.

Overexpression of KLF4 also weakened the anti-tumour effect of CHRM3-AS2 silencing in mice. Silencing of CHRM3-AS2 expression inhibited the malignant progression of glioma by regulating miR-370-5p/KLF4 expression.

Collectively, KLF14 suppressed breast cancer cell invasion and M2 macrophage polarization through modulating SOCS3/RhoA/Rock/STAT3 signaling, and these findings would provide a new potential target against breast cancer.

Our study revealed that OTUD1 suppresses NSCLC progression by mediating KLF4 stabilization, which suggests a potential gene target for the future treatment of NSCLC.

Besides, cell malignant phenotypes could be inhibited through reducing miR-135b-5p level, but they were restored by GPRC5A. Our results stressed that KLF4, as a vital target of miR-135b-5p, could influence promoter region of GPRC5A, thus affecting the malignant progression of pancreatic cancer.

LINC00852 may be a prognostic biomarker for NSCLC. The epigenetic signaling pathway of LINC00852/hsa-miR-145-5p/KLF4 may be considered as a novel molecular target to fight NSCLC.

The level of KLF4 is correlated with the sensitivity of MCF-7 and T47D cells to PTX. DIM could enhance the antitumor efficacy of PTX on MCF-7 and T47D cells by regulating DNMT1 and KLF4.