MicroRNA-145 Regulates OCT4, SOX2, and KLF4 and Represses Pluripotency in Human Embryonic Stem Cells

Xu, Na; Papagiannakopoulos, Thales; Pan, Guangjin; Thomson, James A.; Kosik, Kenneth S.

doi:10.1016/j.cell.2009.02.038

Cited by 1,009 publications

(730 citation statements)

References 48 publications

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“…The monoclonal antibodies DO1 or 1801 were used to detect p53. Polyclonal antibodies were purchased from either Santa Cruz Biotechnology, Inc. (Santa Cruz, CA) (sc-502, anti-p21; C- 19) qRT-PCR to Assess Expression Changes of Mature MicroRNAs-HCT116 cells were plated to ϳ50% confluence (24 h) in 6-well plates with at least three replicates per sample. At 24 h, cells were left untreated or were treated with 0.22 M daunorubicin (Sigma).…”

Section: Methodsmentioning

confidence: 99%

p53-dependent Induction of PVT1 and miR-1204

Barsotti

Beckerman

Laptenko

et al. 2012

Journal of Biological Chemistry

168

165

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Section: Methodsmentioning

confidence: 99%

p53-dependent Induction of PVT1 and miR-1204

Barsotti

Beckerman

Laptenko

et al. 2012

Journal of Biological Chemistry

168

165

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“…It is conceivable that miRNAs can act on a pool of RNAs transcribed earlier, which is also relevant during cell fate changes, and thereby influence the switch to new gene expression programs. Importantly, miRNAs modulate differentiation by targeting pluripotency transcription factors [58,59].…”

Section: Are We There Yet? Are Es and Ips Cells Equivalent?mentioning

confidence: 99%

Reprogramming to pluripotency: stepwise resetting of the epigenetic landscape

2011

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In 2006, the "wall came down" that limited the experimental conversion of differentiated cells into the pluripotent state. In a landmark report, Shinya Yamanaka's group described that a handful of transcription factors (Oct4, Sox2, Klf4 and c-Myc) can convert a differentiated cell back to pluripotency over the course of a few weeks, thus reprograming them into induced pluripotent stem (iPS) cells. The birth of iPS cells started off a rush among researchers to increase the efficiency of the reprogramming process, to reveal the underlying mechanistic events, and allowed the generation of patient-and disease-specific human iPS cells, which have the potential to be converted into relevant specialized cell types for replacement therapies and disease modeling. This review addresses the steps involved in resetting the epigenetic landscape during reprogramming. Apparently, defined events occur during the course of the reprogramming process. Immediately, upon expression of the reprogramming factors, some cells start to divide faster and quickly begin to lose their differentiated cell characteristics with robust downregulation of somatic genes. Only a subset of cells continue to upregulate the embryonic expression program, and finally, pluripotency genes are upregulated establishing an embryonic stem cell-like transcriptome and epigenome with pluripotent capabilities. Understanding reprogramming to pluripotency will inform mechanistic studies of lineage switching, in which differentiated cells from one lineage can be directly reprogrammed into another without going through a pluripotent intermediate.

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“…Moreover, it has been reported to inhibit metastasis of several cancers, including esophageal (28), pancreatic (23), and colorectal cancer cells (29). In addition, KLF4 mRNA is targeted by miR-145 (30), implicating the post-transcriptional control of KLF4.…”

mentioning

confidence: 99%

MicroRNA-10b Promotes Migration and Invasion through KLF4 in Human Esophageal Cancer Cell Lines

Tian

Luo

Cai

et al. 2010

Journal of Biological Chemistry

275

207

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Recently, microRNAs have emerged as regulators of cancer metastasis through acting on multiple signaling pathways involved in metastasis. In this study, we have analyzed the level of miR-10b and cell motility and invasiveness in several human esophageal squamous cell carcinoma cell lines. Our results reveal a significant correlation of miR-10b level with cell motility and invasiveness. Overexpression of miR-10b in KYSE140 cells increased cell motility and invasiveness, whereas inhibition of miR-10b in EC9706 cells reduced cell invasiveness, although it did not alter cell motility. Additionally, we identified KLF4, a known tumor suppressor gene that has been reported to suppress esophageal cancer cell migration and invasion, as a direct target of miR-10b. MicroRNAs, a class of small noncoding RNAs, have been identified as a new kind of gene expression regulators through targeting mRNAs for translational repression or cleavage (1-3). Lately, emerging evidence suggests important roles for miRNAs 2 in apoptosis (4), hematopoietic development (5), cell proliferation (6), skin morphogenesis (7), and neural development (8). Deregulation of miRNAs has also been reported in a variety of tumors, including breast cancer, leukemia, lung cancer, and colon cancer (9 -11), which indicated a significant correlation between miRNAs and human malignancy. miRNA expression profiling in esophageal cancers revealed a distinct miRNA signature (12, 13), and some miRNAs showed correlation with several clinicopathologic parameters (13). Furthermore, miR-21 is reported to regulate the proliferation and invasion in ESCC (14), and the miR-106b-25 polycistron is activated by genomic amplification and is potentially involved in esophageal neoplastic progression (15), providing evidence of a causal role for miRNAs in esophageal cancer development.Recent studies show that miRNAs may act as activators or inhibitors of tumor metastasis by acting on multiple signaling pathways involved in metastasis (16 -18). Ma et al. (16) found that miR-10b initiates invasion and metastasis in breast cancer. miR10b, induced by the prometastatic transcription factor TWIST1, proceeds to inhibit translation of mRNA of HOXD10, a transcription factor already known for its roles in cell motility (19), resulting in increased expression of a pro-metastatic gene, RHOC. This study has provided the first evidence for a role of miRNA in tumor metastasis. Subsequently several additional miRNAs have been reported to act on various steps of metastasis (17, 18).Krüppel-like factor 4 (KLF4), a zinc finger protein of the Krüp-pel-like factor family, plays a role in cell cycle regulation, differentiation, and rises in response to DNA damage, serum starvation, and contact inhibition (20, 21). In line with these studies, the loss of KLF4 expression has been reported in several human tumors, including colorectal, stomach, esophageal, and bladder cancers (22-25), which indicates its tumor suppressor role. However, KLF4 also exhibits oncogenic properties. Overexpression of KLF4 could b...

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MicroRNA-145 Regulates OCT4, SOX2, and KLF4 and Represses Pluripotency in Human Embryonic Stem Cells

Cited by 1,009 publications

References 48 publications

p53-dependent Induction of PVT1 and miR-1204

p53-dependent Induction of PVT1 and miR-1204

Reprogramming to pluripotency: stepwise resetting of the epigenetic landscape

MicroRNA-10b Promotes Migration and Invasion through KLF4 in Human Esophageal Cancer Cell Lines

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