High expression of Krüppel‐like factor 5 is associated with poor prognosis in patients with colorectal cancer

Takagi, Yutaka; Sakai, Nozomu; Yoshitomi, Hideyuki; Furukawa, Katsunori; Takayashiki, Tsukasa; Kuboki, Satoshi; Takano, Shigetsugu; Suzuki, Daisuke; Kagawa, Shingo; Mishima, Takashi; Nakadai, Eri; Miyauchi, Hideaki; Matsubara, Hisahiro; Ohtsuka, Masayuki

doi:10.1111/cas.14411

Cited by 36 publications

(42 citation statements)

References 43 publications

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“…S8A, B ). Moreover, we and another group recently showed that the treatment of miR-4711-5p targeting to the 3’-UTR of KLF5 mRNA or KLF5 -siRNA attenuated the CSC properties in CRC cell lines [ 10 , 11 ]. We also showed in this study that high KLF5 expression in CRC clinical samples was correlated with poor prognosis, which is consistent with other studies [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

“…Cancer stem cells (CSCs) are defined as a subpopulation of cancer cells with a self-renewal capacity and multilineage potency and considered a source of tumour recurrence and metastasis [ 9 ]. KLF5 is associated with CSC-like properties because KLF5 knockdown suppressed sphere-formation activity in colorectal cancer (CRC) cell lines [ 10 ]. We also reported that miR-4711-5p, which directly targets the 3’-untranslated regions (3’-UTRs) of KLF5 , suppressed CSC properties in CRC cell lines [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

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A stem cell marker KLF5 regulates CCAT1 via three-dimensional genome structure in colorectal cancer cells

et al. 2021

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Background KLF5 plays a crucial role in stem cells of colorectum in cooperation with Lgr5 gene. In this study, we aimed to explicate a regulatory mechanism of the KLF5 gene product from a view of three-dimensional genome structure in colorectal cancer (CRC). Methods In vitro engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP)-seq method was used to identify the regions that bind to the KLF5 promoter. Results We revealed that the KLF5 promoter region interacted with the KLF5 enhancer region as well as the transcription start site (TSS) region of the Colon Cancer Associated Transcript 1 (CCAT1) gene. Notably, the heterodeletion mutants of KLF5 enhancer impaired the cancer stem-like properties of CRC cells. The KLF5 protein participated in the core-regulatory circuitry together with co-factors (BRD4, MED1, and RAD21), which constructs the three-dimensional genome structures consisting of KLF5 promoter, enhancer and CCAT1 TSS region. In vitro analysis indicated that KLF5 regulated CCAT1 expression and we found that CCAT1 expression was highly correlated with KLF5 expression in CRC clinical samples. Conclusions Our data propose the mechanistic insight that the KLF5 protein constructs the core-regulatory circuitry with co-factors in the three-dimensional genome structure and coordinately regulates KLF5 and CCAT1 expression in CRC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A stem cell marker KLF5 regulates CCAT1 via three-dimensional genome structure in colorectal cancer cells

et al. 2021

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“…KLF5 is also a critical mediator of the oncogene H-RAS (18,19) and tumor suppressor APC (20,21). Increases the expression of KLF5 is associated with poor prognosis (22). In vitro knockdown experiments have shown that KLF5 interacts with b-catenin and localizes to the nucleus where the complex transactivates target genes, such as CCND1 and c-MYC (20,22).…”

Section: Discussionmentioning

confidence: 99%

“…Increases the expression of KLF5 is associated with poor prognosis (22). In vitro knockdown experiments have shown that KLF5 interacts with b-catenin and localizes to the nucleus where the complex transactivates target genes, such as CCND1 and c-MYC (20,22). Genome-wide association studies identified the regulatory region of KLF5 as a risk locus for endometrial cancer (23).…”

Section: Discussionmentioning

confidence: 99%

Krüppel‑like factor 5 is upregulated and induces cell proliferation in endometrial cancer

et al. 2021

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Krüppel-like factor 5 (KLF5) is involved in various cellular processes, such as cell proliferation and survival. KLF5 has been implicated in cancer pathology. The aim of the present study was to investigate the expression levels and function of KLF5 in endometrial cancer. A total of 30 patients, including 12 patients with endometrial cancer and 18 with benign gynecological diseases (controls), were enrolled at Tokyo Medical University (Tokyo, Japan) between March 2017 and May 2018. Endometrial cancer and control endometrium tissues were collected, and the expression levels of KLF5 were determined using reverse transcription-quantitative PCR, western blotting and immunohistochemistry. For the functional analyses of KLF5 in endometrial cancer, the present study employed a loss-of-function strategy in the human endometrial cancer cell lines in vitro. Ishikawa and HEC1 cells were transduced with lentiviral constructs expressing shRNAs targeting KLF5. MTT and TUNEL assays were performed in cells after knockdown to analyze the role of KLF5 in cell proliferation and survival. The results revealed that the mRNA and protein expression levels of KLF5 were increased in endometrial cancer tissues. In vitro analyses demonstrated that depletion of KLF5 inhibited cell proliferation and decreased the expression levels of cyclin E1. However, silencing KLF5 did not induce cell death. Overall, these results indicated that KLF5 may be crucial in the tumorigenesis of endometrial cancer and has potential as a therapeutic target.

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“…Krüppel like factor 5 (KLF5) is a zinc nger transcription factor that contributes to tumor suppression in NPC [8]. However, KLF5 has an oncogenic role in certain types of cancer, such as pancreatic cancer, breast cancer, cervical cancer and colorectal cancer [9][10][11][12]. The miR-493-5p represses the metastasis and proliferation of osteosarcoma cells by targeting KLF5 [13].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-145-5p modulates KLF5 and inhibits the migration and invasion in nasopharyngeal carcinoma

Yuan

Hsu

Huang

et al. 2021

Preprint

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Human krüppel like factor 5 (KLF5) is a zinc finger transcription factor, which contributes to tumor suppression in nasopharyngeal carcinoma (NPC). However, the precise role of KLF5 in NPC remains poorly understood. In the present study, the association between KLF5 and miR-145-5p in NPC cells was elucidated. Cellular proliferation was detected using the WST-1 colorimetric assay. Cellular migration and invasion were studied using wound healing assays and the ECMatrix cell invasion assay, respectively. The protein expression was examined by western blot. Transfection was subsequently performed for generating NPC cells overexpressing KLF5 and miR-145-5p. The upregulation of KLF5 or miR-145-5p inhibited the migration and invasion of NPC cells. It was observed that miR-145-5p could induce the expression of the KLF5 protein in the NPC cell lines. Additionally, the activity of the migration marker, focal adhesion kinase (FAK), was suppressed following the overexpression of miR-145-5p and KLF5 in NPC cells. The results of this study indicated that miR-145-5p may repress the migration and invasion of NPC cells via KLF5, and could be a potential therapeutic target for NPC.

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High expression of Krüppel‐like factor 5 is associated with poor prognosis in patients with colorectal cancer

Cited by 36 publications

References 43 publications

A stem cell marker KLF5 regulates CCAT1 via three-dimensional genome structure in colorectal cancer cells

A stem cell marker KLF5 regulates CCAT1 via three-dimensional genome structure in colorectal cancer cells

Krüppel‑like factor 5 is upregulated and induces cell proliferation in endometrial cancer

MicroRNA-145-5p modulates KLF5 and inhibits the migration and invasion in nasopharyngeal carcinoma

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