The functions and prognostic value of Krüppel‐like factors in breast cancer

Abstract

Background Krüppel‐like factors (KLFs) are zinc finger proteins which participate in transcriptional gene regulation. Although increasing evidence indicate that KLFs are involved in carcinogenesis and progression, its clinical significance and biological function in breast cancer are still limited. Methods We investigated all the expression of KLFs (KLF1-18) at transcriptional levels by using Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA). The mRNA and protein expression levels of KLFs were also determined by using RT-qPCR and immunohistochemistry, respectively. CBioPortal, GeneMANIA and STRING were used to comprehensive analysis of the molecular characteristics of KLFs. The clinical value of prognostic prediction based on the expression of KLFs was determined by using the KM plotter. The relevant molecular pathways of KLFs were further analyzed by using Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. Finally, we investigated the effect of KLF2 and KLF15 on biological behavior of breast cancer cells in vitro. Results The expression of KLF2/4/6/8/9/11/15 was significantly down-regulated in breast cancer. The patients with high KLF2, KLF4 or KLF15 expression had a better outcome, while patients with high KLF8 or KLF11 had a poor prognosis. Furthermore, our results showed that KLF2 or KLF15 can be used as a prognostic factor independent on the other KLFs in patients with breast cancer. Overexpression of KLF2 or KLF15 inhibited cell proliferation and migration, and blocked cell cycle at G0/G1 phase, resulting in cell apoptosis. Conclusions KLF2 and KLF15 function as tumor suppressors in breast cancer and are potential biomarkers for prognostic prediction in patients with breast cancer.

miR‐92a‐3p promotes breast cancer proliferation by regulating the KLF2/BIRC5 axis

“…KM plotter was used to investigate the correlation between miR-92a-3p and prognosis, and showed that the overexpression of miR-92a led to poor clinical outcomes (Figure S1). KLF2 overexpression was related to better prognosis in our previous study, 12 which was contrary to the result of miR-92a. The expression level of miR-92a-3p was upregulated in all breast cancer cell lines compared with normal breast cells (Figure 1c).…”

“…The expression level of miR‐92a‐3p was upregulated in all breast cancer cell lines compared with normal breast cells (Figure 1c). However, KLF2 was found to be remarkably downregulated in breast cancer cell lines compared with MCF‐10A cells in our previous study 12 . Moreover, qRT‐PCR (Figure 1d) and western blot (Figure 1e) revealed that the expression level of KLF2 was significantly decreased in miR‐92a‐3p‐overexpressed MCF‐7 and T47D cell lines but increased in miR‐92a‐3p‐depleted CAL‐51 and MDA‐231 cells.…”

“…However, KLF2 was found to be remarkably downregulated in breast cancer cell lines compared with MCF‐10A cells in our previous study. 12 Moreover, qRT‐PCR (Figure 1d ) and western blot (Figure 1e ) revealed that the expression level of KLF2 was significantly decreased in miR‐92a‐3p‐overexpressed MCF‐7 and T47D cell lines but increased in miR‐92a‐3p‐depleted CAL‐51 and MDA‐231 cells. The putative binding site of miR‐92a‐3p with KLF2 was predicted by TargetScan (Figure 1f ).…”

“…KLFs can behave as both oncogenes and tumor suppressors 8 . In our previous study, we analyzed the expression pattern of KLFs and identified KLF2/15 as tumor suppressors that inhibited cell invasion and proliferation in breast cancer 12 . However, the underlying mechanism of KLFs is still uncertain and requires further investigation.…”

SP and KLF Transcription Factors in Cancer Metabolism

“…In breast cancer, cancer stem-like cells (CSC) can alter energy metabolism to focus on the hexosamine biosynthesis pathway (HBP) to permit increased cell proliferation [ 100 , 101 ]. High KLF8 expression is associated with poor prognosis of breast cancer patients and was found to play a role in the HBP [ 102 , 103 ]. About 2–5% of glucose and glutamine transported into the cell enter the HBP to generate UDP-GlcNAc.…”