miR-4711-5p regulates cancer stemness and cell cycle progression via KLF5, MDM2 and TFDP1 in colon cancer cells

Morimoto, Yoshihiro; Mizushima, Tsunekazu; Wu, Xin; Okuzaki, Daisuke; Yokoyama, Yuhki; Inoue, Akira; Hata, Tsuyoshi; Hirose, Haruka; Qian, Yamin; Wang, Jiaqi; Miyoshi, Norikatsu; Takahashi, Hidekazu; Haraguchi, Naotsugu; Matsuda, Chu; Doki, Yuichiro; Mori, Masaki; Yamamoto, Hirofumi

doi:10.1038/s41416-020-0758-1

Cited by 44 publications

(46 citation statements)

References 53 publications

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“…39 MAZ was thought to act as a therapeutic target for aerobic glycolysis and the progression of neuroblastoma 40 and prostate cancer bone metastasis. 41 TFDP1 was involved in colon cancer stemness and cell cycle progression 42 and in the endometrium of women with deep infiltrating endometriosis (DIE). 43 The relevant microRNA and interactions between hub genes and core TFs MAZ and TFDP1 had already been verified, suggesting they may participate in the formation of progestin resistance, while the detailed regulated mechanisms between TFs and hub genes needed to be further confirmed both in vitro and vivo.…”

Section: Dovepressmentioning

confidence: 99%

<p>Identification and Validation of MSX1 as a Key Candidate for Progestin Resistance in Endometrial Cancer</p>

Yang

Cui

Huang

et al. 2020

OTT

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Section: Dovepressmentioning

confidence: 99%

<p>Identification and Validation of MSX1 as a Key Candidate for Progestin Resistance in Endometrial Cancer</p>

Yang

Cui

Huang

et al. 2020

OTT

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“…Regulatory ncRNAs such as miRNAs and lncRNAs have been shown to regulate the expression, stability, and subcellular location of PCGs in a various number of biological processes [81,82]. Nowadays, several studies about the association between miRNAs and KLF5 have been published [83][84][85]. For example, miR-5195-3p inhibits the proliferation and invasion of human bladder cancer cells by directly targeting KLF5 [83].…”

Section: Discussionmentioning

confidence: 99%

Network analysis of KLF5 targets showing the potential oncogenic role of SNHG12 in colorectal cancer

Liao¹,

Chen²,

Zhang³

et al. 2020

Cancer Cell Int

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Background KLF5 is a member of the Kruppel-like factor, subfamily of zinc finger proteins that are involved in cancers. KLF5 functions as a transcription factor and regulates the diverse protein-coding genes (PCGs) in colorectal cancer (CRC). However, the long non-coding RNAs (lncRNAs) regulated by KLF5 in CRC are currently unknown. Methods In this study, we first designed a computational pipeline to determine the PCG and lncRNA targets of KLF5 in CRC. Then we analyzed the motif pattern of the binding regions for the lncRNA targets. The regulatory co-factors of KLF5 were then searched for through bioinformatics analysis. We also constructed a regulatory network for KLF5 and annotated its functions. Finally, one of the KLF5 lncRNA targets, SNHG12, was selected to further explore its expression pattern and functions in CRC. Results We were able to identify 19 lncRNA targets of KLF5 and found that the motifs of the lncRNA binding sites were GC-enriched. Next, we pinpointed the transcription factors AR and HSF1 as the regulatory co-factors of KLF5 through bioinformatics analysis. Then, through the analysis of the regulatory network, we found that KLF5 may be involved in DNA replication, DNA repair, and the cell cycle. Furthermore, in the cell cycle module, the SNHG12 up-regulating expression pattern was verified in the CRC cell lines and tissues, associating it to CRC invasion and distal metastasis. This indicates that SNHG12 may play a critical part in CRC tumorigenesis and progression. Additionally, expression of SNHG12 was found to be down-regulated in CRC cell lines when KLF5 expression was knocked-down by siRNA; and a strong correlation was observed between the expression levels of SNHG12 and KLF5, further alluding to their regulatory relationship. Conclusions In conclusion, the network analysis of KLF5 targets indicates that SNHG12 may be a significant lncRNA in CRC.

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“…TFDP1 was involved in colon cancer stemness and cell cycle progression [35] and in the endometrium of women with deep infiltrating endometriosis (DIE) [36]. The relevant microRNA and interactions between hub genes and core TFs MAZ and TFDP1 had already been verified, suggesting they may participate in the formation of progestin resistance, while the detailed regulated mechanisms between TFs and hub genes needed to be further confirmed both in vitro and vivo.…”

Section: Discussionmentioning

confidence: 99%

Screening and identification of MSX1 for predicting progestin resistance in endometrial cancer

Yang

Cui

Huang

et al. 2020

Preprint

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Background: Progestin resistance is a critical obstacle for endometrial conservative therapy. Therefore, the studies to acquire a more comprehensive understanding of the mechanisms and specific biomarkers to predict progestin resistance are very important. However, the pivotal roles of essential molecules of progestin resistance are still unexplored.Methods: We downloaded GSE121367 with gene expression profiles of medroxyprogesterone acetate (MPA) resistant and sensitive cell lines from the GEO database. The "limma" R language package was applied to identify differentially expressed genes (DEGs). Gene ontology and pathway enrichment analysis was performed through the database of DAVID. Meanwhile, we conducted GSEA analysis to identify pathway enrichments. Protein-protein interaction construction of top genes was conducted to screen hub genes by STRING and visualized in Cytoscape. A high connectivity degree of hub genes were picked out to perform the differential expression, methylation validation and overall survival analysis in the Gene Expression Profiling Interactive Analysis database, Human Protein Atlas database and Kaplan-Meier plotter online tool, respectively. In addition, microRNAs and upstream transcription factors of hub genes were predicted by miRTarBase and Network Analyst database.Results: A total number of 3282 differentially expressed genes were identified. Functional enrichment analysis demonstrated that these genes were mostly enriched in negative regulation of DNA binding, chronic inflammatory response and cell adhesion molecules pathway. We screened out ten hub genes including CDH1, JAG1, PTGES, EPCAM, CNTNAP2, TBX1, MSX1, KRT19, OAS1 and DAB2 among different groups. The genomic alteration rates of hub genes were low based on the current uterine corpus endometrial carcinoma sample sets. Their relevant microRNA and transcription factor were detected and has-miR-335-5p, has-miR-124-3p, MAZ and TFDP1 were the most prominent. The methylation status of CDH1, JAG1, EPCAM and MSX1 were decreased, corresponding to their high protein expression in endometrial cancers, which also indicated better overall survival. The homeobox protein of MSX1 showed significantly tissue specificity.Conclusions: Our study identified ten hub genes associated with progestin resistance of endometrial cancer and screened out the gene of MSX1 which promised to be the specific indicator. This would

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miR-4711-5p regulates cancer stemness and cell cycle progression via KLF5, MDM2 and TFDP1 in colon cancer cells

Cited by 44 publications

References 53 publications

<p>Identification and Validation of MSX1 as a Key Candidate for Progestin Resistance in Endometrial Cancer</p>

<p>Identification and Validation of MSX1 as a Key Candidate for Progestin Resistance in Endometrial Cancer</p>

Network analysis of KLF5 targets showing the potential oncogenic role of SNHG12 in colorectal cancer

Screening and identification of MSX1 for predicting progestin resistance in endometrial cancer

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