KLF4, a miR-32-5p targeted gene, promotes cisplatin-induced apoptosis by upregulating BIK expression in prostate cancer

Abstract

BackgroundChemotherapeutic insensitivity remains a big challenge in prostate cancer treatment. Recently, increasing evidence has indicated that KLF4 plays a key role in prostate cancer. However, the potential biological role of KLF4 in Chemotherapeutic insensitivity of prostate cancer is still unknown.MethodsThe role of KLF4 in cisplatin-induced apoptosis was detected by western blotting and a cell counting kit (CCK8). The potential molecular mechanism of KLF4 in regulating prostate cancer chemosensitivity was investigated by RNA sequencing analysis, q-RT-PCR, western blotting and chromatin immunoprecipitation (ChIP). The expression level of KLF4 mediated by miR-32-5p was confirmed by bioinformatic analysis and luciferase assays.ResultsHere, we found that KLF4 was induced by cisplatin in prostate cancer cells and that the increase in KLF4 promoted cell apoptosis. Further mechanistic studies revealed that KLF4 directly bound to the promoter of BIK, facilitating its transcription. Additionally, we also found that the gene encoding KLF4 was a direct target of miR-32-5p. The downregulation of miR-32-5p in response to cisplatin treatment promoted KLF4 expression, which resulted in a increase in the chemosensitivity of prostate cancer.ConclusionThus, our data revealed that KLF4 is an essential regulator in cisplatin-induced apoptosis, and the miR-32-5p-KLF4-BIK signalling axis plays an important role in prostate cancer chemosensitivity.Electronic supplementary materialThe online version of this article (10.1186/s12964-018-0270-x) contains supplementary material, which is available to authorized users.

Recent Discoveries on the Involvement of Krüppel-Like Factor 4 in the Most Common Cancer Types

“…Nevertheless, KLF4 is important in regulating response to many known drugs [ 1 ]. These include cetuximab [ 23 ], cisplatin [ 19 , 43 , 72 , 84 , 102 ], gefitinib [ 79 ], glibenclamide [ 78 ], mesalazine [ 22 ] and Sijunzi decoction [ 20 ].…”

“…In prostate cancer, the expression of KLF4 is regulated by miR-7, miR-32-5p, miR-148-3p and miR-152-3p [ 94 , 95 , 102 ]. KLF4 and miR-7 form an auto-regulatory feedback loop, in which KLF4 positively regulates the expression of miR-7 while miR-7 negatively regulates the expression of KLF4 [ 94 ].…”

“…KLF4 positively regulates the expression of miR-1, BCL2-interacting killer (BIK) and insulin-like growth factor 2 (IGF2) in prostate cancer [ 97 , 102 , 104 ]. The latter occurs in response to cisplatin treatment, thus promoting cisplatin-induced apoptosis in prostate cancer [ 102 ]. Apoptosis is triggered by miR-32-5p, which is downregulated upon cisplatin treatment and inhibits the expression of KLF4.…”

“…Apoptosis is triggered by miR-32-5p, which is downregulated upon cisplatin treatment and inhibits the expression of KLF4. Following the administration of cisplatin, KLF4 levels are increased, which leads to increased production of BIK and apoptosis [ 102 ]. KLF4 is very important in androgen receptor (AR) signaling [ 97 ].…”

Long non‐coding RNA LINC00673 silencing inhibits proliferation and drug resistance of prostate cancer cells via decreasing KLF4 promoter methylation

“…Furthermore, differential expressions of LINC00673 have been documented in numerous cancers. 11 Additionally, the expression of KLF4 stimulated by lysophosphatidic acid has been revealed to be involved in the proliferation and migration abilities of prostate cancer cells. 7,8 In addition, Ba et al suggested that LINC00673 could potentiate the progression of gastric cancer, partly owing to its suppressive roles in the expression of Kruppel-like factor 4 (KLF4).…”