KLF5 promotes apoptosis induced by phorbol ester as an effector of the autocrine factor TNFα in LNCaP prostate cancer cells

Abstract

Abstract. Krüppel-like factor 5 (KLF5) is frequently deleted and inactivated in prostate cancer, and exerts tumor-suppressing function in prostate cancer cells. However, the function of KLF5 in the apoptosis of prostate cancer cells remains unclear. In the present study, the effect of KLF5 on phorbol 12-myristate 13-acetate (PMA)-induced apoptosis was investigated in prostate cancer LNCaP cells. It was demonstrated that PMA induced the expression of KLF5 at the mRNA and protein level. To identify whether KLF5 regulates the activity of the downstream pathway, stable KLF5 knockdown or overexpression cell lines were constructed with lentivirus harboring shRNA targeting KLF5 or full-length KLF5 in LNCaP cells. Knockdown of KLF5 significantly decreased PMA-induced apoptosis, while cell apoptosis was significantly increased following KLF5 overexpression compared with the corresponding control groups. Consistently, expression of cleaved poly(ADP-ribose) polymerase and caspase-3 induced by PMA was decreased following KLF5 knockdown and increased following KLF5 overexpression. Using the control medium from cells treated with PMA, it was demonstrated that KLF5 is required for the control medium to induce apoptosis. c-Jun N-terminal kinase (JNK) activity is essential for the apoptosis induced by PMA. It was revealed that knockdown of KLF5 decreased, while overexpression of KLF5 increased the phosphorylation of JNK induced by PMA and control medium treatment. Furthermore, inhibition of tumor necrosis factor α (TNFα) decreased KLF5 expression and significantly decreased cell apoptosis induced by PMA, and control medium. This data indicates that KLF5 is essential for the apoptosis induced by PMA in LNCaP prostate cancer cells. Furthermore, KLF5 is essential for activity of the autocrine factor TNFα, which is secreted by cells treated with PMA and mediates the function of PMA-induced apoptosis through regulating the activity of JNK signaling pathway. These results provide novel insights into the complexity of the signaling pathways regulating apoptosis in prostate cancer cells, which could aid in the development of novel treatments for patients with prostate cancer.

miR‐145‐5p affects the differentiation of gastric cancer by targeting KLF5 directly

“…RNAs of approximately 21-25 nucleotides in sequence length, which act as posttranscriptional modulators of gene expression in cancer progression by binding to the 3′-UTR of target mRNA to induce mRNA degradation or translational repression (Bartel, 2004;Calin & Croce, 2006;Macfarlane & Murphy, 2010). miR-145-5p was predicted to KLF5 has important and context-dependent functions in both promoting and suppressing cell proliferation (Diakiw et al, 2013;Jia, Zhou, & Liang, 2016;Ma, Chang, & Zhao, 2017;Shi, Jia, & Hui, 2017;Xing, Ci, & Sun, 2014;Yang et al, 2017a). However, the clinical significance of KLF5 protein in gastric cancer has remained largely unknown.…”

Krüppel-like factor 5 accelerates the pathogenesis of Alzheimer’s disease via BACE1-mediated APP processing

“…The ChIP assay was performed to identify whether site 4 was the actual binding site of KLF5 in the BACE1 promoter. The KLF5 expression is rapidly induced in NIH3T3 and LNCaP cells exposed to phorbol 12-myristate 13-acetate (PMA), which promotes the BACE1 expression in U937 cells [ 18 – 20 ]. Thus, SH-SY5Y cells, which are commonly used in studying AD, were stimulated with PMA in our study to investigate whether KLF5 and BACE1 expression could be induced by PMA stimulation.…”

Medical molecules of waste Chinese buckeye seed from pharmacy

“…By introducing a furfural moiety into the fluorescein molecular skeleton, a fluorescent probe (Fluo-HMF) was developed as a bioimaging fluorescent probe for some related allergic mechanism studies [35]. Phorbol: Up-regulation of PKC plays a physiological role in regulating uterine contracture after delivery, and a shift from staged to strong tonic contraction may contribute to postpartum hemostasis [36], phorbol-ester inhibits metastatic spread and occurrence of melanoma [37], phorbol-ester also controls protease expression [38], KLF5 promotes phorbol ester-induced apoptosis and exerts tumor suppressor function in prostate cancer cells [39]. As a pharmaceutical intermediate, chemical raw material and food additive, Dihydroxyacetone can synthesize some medicines for treating cardiovascular diseases.…”