Dataset Information

The Clinical Relevance and Function of Kruppel-Like Factor 16 in Breast Cancer.

ABSTRACT: Background:Krüppel-like factor 16 (KLF16), a member of the KLF family, is involved in metabolism and regulation of the endocrine system and has emerging roles in tumor progression. However, the expression of KLF16 and its role in breast cancer are elusive. Methods:We investigated the expression and prognostic value of KLFs in breast cancer using data acquired from the TCGA BRCA dataset and the Kaplan-Meier plotter dataset. The protein levels of KLF16 in breast specimens were detected by immunohistochemistry (IHC). KLF16 silencing using shRNAs was performed to explore the effects of KLF16 on breast cancer cell growth, migration, and invasion. The expression of EMT markers in cells manipulated for KLF16 expression was assessed by Western blotting. Results:Using publicly available dataset and specimens from breast cancer patients, we found that the expression levels of KLF16 were significantly higher in tumor tissues and that high levels of KLF16 were associated with poor prognosis in breast cancer patients. Moreover, KLF16 expression levels had relation to several clinicopathological parameters of breast cancer, including the molecular subtype and histological grade. Importantly, knockdown of KLF16 dramatically suppressed cell proliferation both in vitro and in vivo. Also, KLF16 deletion impaired migration, and invasion in breast cancer cells, and suppressed epithelial-mesenchymal transition (EMT). Conclusion:Our results suggest that KLF16 has important oncogenic functions in breast cancer and that the expression levels of KLF16 are associated with prognosis in breast cancer patients. Our findings also suggest that KLF16 is involved in proliferation, migration, and invasion in breast cancer cells. Thus, KLF16 might be a promising prognostic marker and a therapeutic target for breast cancer.

SUBMITTER: Bang S

PROVIDER: S-EPMC7419641 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The Clinical Relevance and Function of Krüppel-Like Factor 16 in Breast Cancer.

Bang Soyeon S Li Junhong J Zhang Meiqin M Cui Renjie R Wu Xingwen X Xin Zhaochen Z Ma Duan D Zhang Jin J Zhang Hongwei H

Cancer management and research 20200727

<h4>Background</h4>Krüppel-like factor 16 (KLF16), a member of the KLF family, is involved in metabolism and regulation of the endocrine system and has emerging roles in tumor progression. However, the expression of KLF16 and its role in breast cancer are elusive.<h4>Methods</h4>We investigated the expression and prognostic value of KLFs in breast cancer using data acquired from the TCGA BRCA dataset and the Kaplan-Meier plotter dataset. The protein levels of KLF16 in breast specimens were detec ...[more]

PMID: 32821156

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Project description:BackgroundRibosomal biogenesis and ribosomal proteins have attracted attention in the context of tumor biology in recent years. Instead of being mere translational machineries, ribosomes might play an active role in tumor initiation and progression. Despite its importance, regulation of ribosomal biogenesis is still not completely understood.MethodsUsing Gene Set Enrichment Analysis of RNA sequencing and proteomical mass spectrometry data in breast cancer cells expressing Krüppel-like factor 7 (KLF7), we identified processes altered by this transcription factor. In silico analyses of a cohort of breast cancer patients in The Cancer Genome Atlas confirmed our finding. We further verified the role of KLF7 the identified ribosomal processes in in vitro assays of mammary carcinoma cell lines and analyses of breast cancer patients' tissue slices.ResultsWe identified the transcription factor Krüppel-like factor 7 (KLF7) as a regulator of ribosomal biogenesis and translation in breast cancer cells and tissue. Highly significant overlapping processes related to ribosomal biogenesis were identified in proteomics and transcriptomics data and confirmed in patients' breast cancer RNA Seq data. Further, nucleoli, the sites of ribosomal biogenesis, were morphologically altered and quantitatively increased in KLF7-expressing cells. Pre-rRNA processing was identified as one potential process affected by KLF7. In addition, an increase in global translation independent from proliferation and transcription was observed upon exogenous KLF7 expression in vitro. Importantly, in a cohort of breast cancer patients, KLF7-expression levels correlated with aggressiveness of the intrinsic breast cancer subtype and tumor grading. Moreover, KLF7 correlated with nucleolar characteristics in human breast tumor tissue, indicating a role for KLF7 in ribosomal biogenesis.ConclusionIn mammary carcinoma, KLF7 is involved in ribosomal biogenesis. Alterations of ribosomal biogenesis has far reaching quantitative and qualitative implications for the proteome of the cancer cells. This might influence the aggressiveness of cancer cells.

Project description:BackgroundCircadian disruption is an emerging driver of breast cancer (BCa), with epidemiological studies linking shift work and chronic jet lag to increased BCa risk. Indeed, several clock genes participate in the gating of mitotic entry, regulation of DNA damage response, and epithelial-to-mesenchymal transition, thus impacting BCa etiology. Dysregulated estrogen (17β-estradiol, E2) and glucocorticoid (GC) signaling prevalent in BCa may further contribute to clock desynchrony by directly regulating the expression and cycling dynamics of genes comprising the local breast oscillator. In this study, we investigated the tumor suppressor gene, Krüppel-like factor 9 (KLF9), as an important point of crosstalk between hormone signaling and the circadian molecular network, and further examine its functional role in BCa.MethodsThrough meta-analysis of publicly available RNA- and ChIP-sequencing datasets from BCa tumor samples and cell lines, and gene expression analysis by RT-qPCR and enhancer- reporter assays, we elucidated the molecular mechanism behind the clock and hormone regulation of KLF9. Lentiviral knockdown and overexpression of KLF9 in three distinct breast epithelial cell lines (MCF10A, MCF7 and MDA-MB-231) was generated to demonstrate the role of KLF9 in orthogonal assays on breast epithelial survival, proliferation, apoptosis, and migration.ResultsWe determined that KLF9 is a direct GC receptor target in mammary epithelial cells, and that induction is likely mediated through coordinate transcriptional activation from multiple GC-responsive enhancers in the KLF9 locus. More interestingly, rhythmic expression of KLF9 in MCF10A cells was abolished in the highly aggressive MDA-MB-231 line. In turn, forced expression of KLF9 altered the baseline and GC/E2-responsive expression of several clock genes, indicating that KLF9 may function as a regulator of the core clock machinery. Characterization of the role of KLF9 using complementary cancer hallmark assays in the context of the hormone-circadian axis revealed that KLF9 plays a tumor-suppressive role in BCa regardless of molecular subtype. KLF9 potentiated the anti-tumorigenic effects of GC in E2 receptor + luminal MCF7 cells, while it restrained GC-enhanced oncogenicity in triple-negative MCF10A and MDA-MB-231 cells.ConclusionsTaken together, our findings support that dysregulation of KLF9 expression and oscillation in BCa impinges on circadian network dynamics, thus ultimately affecting the BCa oncogenic landscape.

Dataset Information

The Clinical Relevance and Function of Kruppel-Like Factor 16 in Breast Cancer.

Publications

The Clinical Relevance and Function of Krüppel-Like Factor 16 in Breast Cancer.

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