Positive Feedback Loop of OCT4 and c-JUN Expedites Cancer Stemness in Liver Cancer

Kuo, Kung‐Kai; Lee, King-Teh; Chen, Ker-Kong; Yang, Ya-Sung; Lin, Ying‐Chu; Tsai, Ming‐Ho; Wuputra, Kenly; Lee, Yen‐Liang; Ku, Chia‐Chen; Miyoshi, Hiroyuki; Nakamura, Yukio; Saito, Shoji; Wu, Chun‐Chieh; Chai, Chee‐Yin; Eckner, Richard; Lin, Chen‐Lung Steve; Wang, Sophie S-W; Wu, Deng‐Chyang; Lin, Chang-Sheng; Yokoyama, Kazunari K.

doi:10.1002/stem.2447

Cited by 48 publications

(60 citation statements)

References 45 publications

(61 reference statements)

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“…41 Elevated expression of KLF-4 in HCC is significantly correlated with poor tumor differentiation, vascular invasion, overall survival, and recurrence-free survival. 22 As a major pluripotent factor, Oct-4 is highly expressed in liver CSCs [42][43][44] and may contribute to the reprogramming of CSCs. Gli-1 is the main transcription factor in hedgehog signaling pathway, which is activated in various chronic liver diseases.…”

Section: Discussionmentioning

confidence: 99%

Activation of pluripotent genes in hepatic progenitor cells in the transition of nonalcoholic steatohepatitis to pre-malignant lesions

Liu

et al. 2017

Laboratory Investigation

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Section: Discussionmentioning

confidence: 99%

Activation of pluripotent genes in hepatic progenitor cells in the transition of nonalcoholic steatohepatitis to pre-malignant lesions

Liu

et al. 2017

Laboratory Investigation

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“…Heterogeneity of cancer cells in the same patient can arise for multiple reasons [58–60]. First, heterogeneity can be generated by stochastic genetic [61] or epigenetic changes [62].…”

Section: Advantages Provided For Cancer Research By Cancer Cell Repromentioning

confidence: 99%

“…These iPSC-like cells were more sensitive to 5-fluorouracil and drugs of differentiation–induction and exhibited reduced tumorigenicity in nonobese diabetic/severe combined immunodeficient mice. Kuo et al [58] found that the positive feedback between OCT4 and c - JUN increased with the onset of cancers. We hypothesized that the positive feedback regulation of OCT4 and c-JUN might promote the generation of liver CSCs.…”

Section: Advantages Provided For Cancer Research By Cancer Cell Repromentioning

confidence: 99%

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Potential application of cell reprogramming techniques for cancer research

Saito

Lin

Nakamura

et al. 2018

Cell. Mol. Life Sci.

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The ability to control the transition from an undifferentiated stem cell to a specific cell fate is one of the key techniques that are required for the application of interventional technologies to regenerative medicine and the treatment of tumors and metastases and of neurodegenerative diseases. Reprogramming technologies, which include somatic cell nuclear transfer, induced pluripotent stem cells, and the direct reprogramming of specific cell lineages, have the potential to alter cell plasticity in translational medicine for cancer treatment. The characterization of cancer stem cells (CSCs), the identification of oncogene and tumor suppressor genes for CSCs, and the epigenetic study of CSCs and their microenvironments are important topics. This review summarizes the application of cell reprogramming technologies to cancer modeling and treatment and discusses possible obstacles, such as genetic and epigenetic alterations in cancer cells, as well as the strategies that can be used to overcome these obstacles to cancer research.

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“…These result further indicate the importance of OCT4 contributing to the development of cancers in a number of ways (18,19). The aim of the present study was to investigate the role of miR-145 in the modulation of cervical cancer cell radiosensitivity, using transfection with miR-145 mimics to upregulate miR-145 in cervical cancer tera cells.…”

Section: Microrna-145 Sensitizes Cervical Cancer Cells To Low-dose Irmentioning

confidence: 91%

MicroRNA-145 sensitizes cervical cancer cells to low-dose irradiation by downregulating OCT4 expression

Yan

Jin

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Poor elucidation of the mechanisms involved in regulating the radiosensitivity of cancers prevents the extensive application of low-dose radiotherapy in clinical settings. The present study was conducted to investigate the role of microRNA-145 (miR-145) in the modulation of cervical cancer cell radiosensitivity, as well as to identify the underlying target of miR-145 during this process. Cervical cancer tera cells were initially exposed to doses of radiation between 1 and 6 Gy before the assessments of the cell viability and apoptosis rate. Irradiation at dose of 1 Gy was screened as optimum dose and used in subsequent experiments. A dual luciferase reporter assay was performed to demonstrate that octamer-binding transcription factor 4 (OCT4) is a target of miR-145 in cervical cancer. Consequently, OCT4 was suggested to be a target of miR-145, as a dual luciferase vector that was ligated to a fragment corresponding to the predicted target site of miR-145 in OCT4 3'-UTR showed an 83% reduction in fluorescence. Following exposure to 1 Gy irradiation, tera cells transfected with miR-145 mimics, which showed downregulation of OCT4 and cyclin D1, had lower cell viability and cell migration rate and higher apoptosis rate compared to non-transfected cells. However, the co-transfection of miR-145 mimics and OCT4 expression vector restored OCT4 and cyclin D1 expression levels and made no significant difference in terms of cell viability, cell migration rate and apoptosis rate. The present results indicate that miR-145 increases the radiosensitivity of cervical cancer cells by silencing OCT4, that cyclin D1 is putatively under the positive regulation of OCT4 and mediates miR-145 function.

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Positive Feedback Loop of OCT4 and c-JUN Expedites Cancer Stemness in Liver Cancer

Cited by 48 publications

References 45 publications

Activation of pluripotent genes in hepatic progenitor cells in the transition of nonalcoholic steatohepatitis to pre-malignant lesions

Activation of pluripotent genes in hepatic progenitor cells in the transition of nonalcoholic steatohepatitis to pre-malignant lesions

Potential application of cell reprogramming techniques for cancer research

MicroRNA-145 sensitizes cervical cancer cells to low-dose irradiation by downregulating OCT4 expression

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