Tumor-suppressive role of Kruppel-like factor 4 (KLF-4) in colorectal cancer

Xiu, Dianhui; Chen, Y; Liu, L; Yang, H S; Liu, G F

doi:10.4238/gmr16019272

Cited by 9 publications

(5 citation statements)

References 27 publications

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“…KLF4 is a conserved zinc finger-containing transcription factor that regulates multiple biological processes [24]. Recently, researchers found that KLF4 acts as a tumor suppressor in various human cancers, such as colorectal cancer, ovarian cancer, HCC, and lung cancer [[25], [26], [27], [28]]. Overexpression of KLF4 recovers cyclin dependent kinase inhibitor 1B (KIP1) protein expression, a negative regulator of the cell cycle, and suppresses the epithelial-mesenchymal transition (EMT) protein, snail family transcriptional repressor 2 (SNAI2) in HCC cells [11].…”

Section: Resultsmentioning

confidence: 99%

SF3B4 is regulated by microRNA-133b and promotes cell proliferation and metastasis in hepatocellular carcinoma

Liu

Pang

et al. 2018

eBioMedicine

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BackgroundSplicing factor 3b subunit 4 (SF3B4) is a splicing factor and potential oncogene in hepatocellular carcinoma (HCC); however, its regulatory mechanism is yet unclear. We aimed to determine the role of SF3B4 in HCC and the underlying mechanism.MethodsTo investigate the association between alternative splicing events and miRNAs, putative miRNAs were screened using TargetScan. Expression levels of and prognostic information for SF3B4 and miRNAs were determined based on public genomic data and clinical samples. Then, we examined the possible roles of SF3B4 and miRNA-133b in HCC cells and a xenograft mouse model. Pearson correlation analysis and in vitro experiments verified SF3B4 as a miRNA-133b target. Protein levels of key targets from the SF3B4 signaling pathway were estimated using western blotting.FindingsThe expression of SF3B4 was upregulated in HCC tissues and cell lines whereas, the expression of miRNA-133b was downregulated. MiRNA-133b negatively regulated the expression of SF3B4. Effects of SF3B4 overexpression were partially abolished by miRNA-133b mimics, confirming that SF3B4 is a target of miRNA-133b. Moreover, molecules associated with SF3B4, including KLF4, KIP1, and SNAI2, were also modulated by miRNA-133b.InterpretationSF3B4 plays a crucial role in HCC and is negatively regulated by miRNA-133b. The miRNA-133b/ SF3B4 axis may serve as a new therapeutic target for HCC treatment.FundChina National Funds for Distinguished Young Scientists (No.81425019), the State Key Program of National Natural Science Foundation of China (No.81730076), Shanghai Science and Technology Committee Program (No.18XD1405300) and Specially-Appointed Professor Fund of Shanghai (GZ2015009). China National Funds for National Natural Science Fund (No.81672899).

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Section: Resultsmentioning

confidence: 99%

SF3B4 is regulated by microRNA-133b and promotes cell proliferation and metastasis in hepatocellular carcinoma

Liu

Pang

et al. 2018

eBioMedicine

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“…KLF4 has a reciprocal regulatory relationship with TGF-β1 and thus affects EMT ( 84 , 87 ). Colorectal cancer specimens with malignant features such as lymphatic metastasis showed low expression of KLF4 ( 156 ). Further studies revealed that KLF4 was negatively correlated with EMT indicators such as TWIST, β-catenin, claudin-1, N-cadherin, and vimentin, implying disrupted intestinal epithelial homeostasis, loss of cell polarity and intercellular junctions ( 157 ).…”

Section: Implications Of Klfs In Tumor Developmentmentioning

confidence: 99%

Krüppel-like factors in tumors: Key regulators and therapeutic avenues

Zhang

Yao

et al. 2023

Front. Oncol.

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Krüppel-like factors (KLFs) are a group of DNA-binding transcriptional regulators with multiple essential functions in various cellular processes, including proliferation, migration, inflammation, and angiogenesis. The aberrant expression of KLFs is often found in tumor tissues and is essential for tumor development. At the molecular level, KLFs regulate multiple signaling pathways and mediate crosstalk among them. Some KLFs may also be molecular switches for specific biological signals, driving their transition from tumor suppressors to promoters. At the histological level, the abnormal expression of KLFs is closely associated with tumor cell stemness, proliferation, apoptosis, and alterations in the tumor microenvironment. Notably, the role of each KLF in tumors varies according to tumor type and different stages of tumor development rather than being invariant. In this review, we focus on the advances in the molecular biology of KLFs, particularly the regulations of several classical signaling pathways by these factors, and the critical role of KLFs in tumor development. We also highlight their strong potential as molecular targets in tumor therapy and suggest potential directions for clinical translational research.

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“…The broadly described role of KLF4 in colorectal cancer (CRC) remains controversial. Many studies have shown that KLF4 plays a tumor-suppressive role in CRC [ 3 ]. The reduced expression of KLF4 in human CRC tissues has been associated with increased growth of CRC cells, lymphatic node metastasis, reduced tumor cell differentiation, and tumor recurrence.…”

Section: Colorectal Cancermentioning

confidence: 99%

“…CRC patients with lymph node metastasis display reduced KLF4 expression. Furthermore, the downregulation of KLF4 is associated with poor prognosis in human CRC patients, decreased overall survival as well as disease-free survival [ 3 ].…”

Section: Colorectal Cancermentioning

confidence: 99%

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

Taracha-Wisniewska

Kotarba

Dworkin

et al. 2020

IJMS

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Krüppel-like factor 4 (KLF4) is a transcription factor highly conserved in evolution. It is particularly well known for its role in inducing pluripotent stem cells. In addition, KLF4 plays many roles in cancer. The results of most studies suggest that KLF4 is a tumor suppressor. However, the functioning of KLF4 is regulated at many levels. These include regulation of transcription, alternative splicing, miRNA, post-translational modifications, subcellular localization, protein stability and interactions with other molecules. Simple experiments aimed at assaying transcript levels or protein levels fail to address this complexity and thus may deliver misleading results. Tumor subtypes are also important; for example, in prostate cancer KLF4 is highly expressed in indolent tumors where it impedes tumor progression, while it is absent from aggressive prostate tumors. KLF4 is important in regulating response to many known drugs, and it also plays a role in tumor microenvironment. More and more information is available about upstream regulators, downstream targets and signaling pathways associated with the involvement of KLF4 in cancer. Furthermore, KLF4 performs critical function in the overall regulation of tissue homeostasis, cellular integrity, and progression towards malignancy. Here we summarize and analyze the latest findings concerning this fascinating transcription factor.

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Tumor-suppressive role of Kruppel-like factor 4 (KLF-4) in colorectal cancer

Cited by 9 publications

References 27 publications

SF3B4 is regulated by microRNA-133b and promotes cell proliferation and metastasis in hepatocellular carcinoma

SF3B4 is regulated by microRNA-133b and promotes cell proliferation and metastasis in hepatocellular carcinoma

Krüppel-like factors in tumors: Key regulators and therapeutic avenues

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

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