Beyond proliferation: KLF5 promotes angiogenesis of bladder cancer through directly regulating VEGFA transcription

Gao, Yang; Wu, Kaijie; Chen, Yule; Zhou, Jiancheng; Du, Chong; Shi, Qi; Xu, Shan; Jia, Jing; Tang, Xiaoshuang; Li, Feng; Hui, Ke; He, Dalin; Guo, Peng

doi:10.18632/oncotarget.6101

Cited by 53 publications

(51 citation statements)

References 35 publications

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“…Therefore, a CNC network was built to further survey the relation of dyregulated lncRNAs and mRNAs. Some major connected mRNAs have been known to be associated with BC, such as VEGFA, PTEN, EGF and FGFR3 [24–26]. We thus deduced that these lncRNAs might be correlated with carcinogenesis of BC by regulating co-expression genes.…”

Section: Discussionmentioning

confidence: 93%

Comprehensive analysis of differentially expressed profiles of lncRNAs and circRNAs with associated co-expression and ceRNA networks in bladder carcinoma

et al. 2016

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Accumulating evidences indicate that long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) play important roles in tumorigenesis. However, the mechanisms remain largely unknown. To explore lncRNAs and circRNAs expression profiling and their biological functions in bladder cancer, we surveyed the lncRNA/circRNA and mRNA expression profiles of bladder cancer and para-cancer tissues using microarray for four patients. Thousands of significantly changed lncRNAs and mRNAs as well as hundreds of circRNAs were identified. Five dysregulated lncRNAs and four mRNAs were confirmed by quantitative real-time PCR in 30 pairs of samples. GO and KEGG pathway enrichment analyses were executed to determine the principal functions of the significantly deregulated genes. Further more, we constructed correlated expression networks including coding-noncoding co-expression (CNC), competing endogenous RNAs (ceRNA), cis regulation, lncRNAs-transcription factor (TF)-mRNA with bioinformatics methods. Co-expression analysis showed lncRNA APLP2 expression is correlated with apoptosis-related genes, including PTEN and TP53INP1. CeRNA network inferred that lncRNA H19 and circRNA MYLK could bind competitively with miRNA-29a-3p increasing target gene DNMT3B, VEGFA and ITGB1 expressions. Moreover, the nearby genes pattern displayed that overexpressing ADAM2 and C8orf4 are cis-regulated by lncRNA RP11-359E19.2, involving in progression of bladder cancer. In addition, lncRNAs-TF-mRNA diagram indicated that lncRNA BC041488 could trans-regulate CDK1 mRNA expression through SRF transcription factor. Taken together, these results suggested lncRNAs and circRNAs could implicate in the pathogenesis and development of bladder cancer. Our findings provide a novel perspective on lncRNAs and circRNAs and lay the foundation for future research of potential roles of lncRNAs and circRNAs in bladder carcinoma.

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Section: Discussionmentioning

confidence: 93%

Comprehensive analysis of differentially expressed profiles of lncRNAs and circRNAs with associated co-expression and ceRNA networks in bladder carcinoma

et al. 2016

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“…It has been reported that KLF5 has a role in different cell processes, including in cell proliferation, cell cycle progression and apoptosis (9)(10)(11). Previous studies have demonstrated that KLF5 acts as an oncogene in different cancer cells, and is a potential tumor suppressor in prostate cancer cells (24).…”

Section: Discussionmentioning

confidence: 99%

“…KLF5 expression in breast cancer exhibit shorter disease-free survival times, and increased KLF5 expression aids in cancer cell proliferation and tumorigenesis (10,12). However, KLF5 has also been demonstrated to act as a tumor suppressor under certain conditions, including JNK activation-induced apoptosis in esophageal squamous cell cancer (13).…”

Section: Klf5 Promotes Apoptosis Induced By Phorbol Ester As An Effecmentioning

confidence: 99%

“…The Krüppel-like transcription factor 5 (KLF5/IKLF/ BTEB2), a type of zinc-finger transcription factor, has important roles in various cellular processes, including in cell proliferation, cell cycle progression and apoptosis (9)(10)(11). Several previous studies have demonstrated that KLF5 acts as an oncogene in different types of cancer, including in bladder and breast cancer (10,12).…”

Section: Introductionmentioning

confidence: 99%

“…Several previous studies have demonstrated that KLF5 acts as an oncogene in different types of cancer, including in bladder and breast cancer (10,12). Patients with increased…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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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.

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KLF5 promotes cell migration by up‐regulating FYN in bladder cancer cells

Gao

et al. 2016

FEBS Letters

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Kr€ uppel-like factor 5 (KLF5) promotes cell proliferation of bladder cancer. However, whether KLF5 regulates other cell processes in bladder cancer is not clear. We found that KLF5 increases cell migration and lamellipodia formation, expression of FYN and phosphorylation of FAK in bladder cancer cells. In addition, KLF5 promotes transcription of FYN through binding to its promoter. FYN overexpression rescues cell migration and lamellipodia formation reduced by KLF5 knockdown. Furthermore, the KLF5/FYN/p-FAK axis is necessary for lysophosphatidic acid (LPA) to promote cell migration. Our findings indicate that both KLF5 and FYN are important in the regulation of cell migration in bladder cancer cells. We propose the KLF5/FYN/p-FAK axis as a potential therapeutic target in bladder cancer.

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Beyond proliferation: KLF5 promotes angiogenesis of bladder cancer through directly regulating VEGFA transcription

Cited by 53 publications

References 35 publications

Comprehensive analysis of differentially expressed profiles of lncRNAs and circRNAs with associated co-expression and ceRNA networks in bladder carcinoma

Comprehensive analysis of differentially expressed profiles of lncRNAs and circRNAs with associated co-expression and ceRNA networks in bladder carcinoma

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

KLF5 promotes cell migration by up‐regulating FYN in bladder cancer cells

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