Reprogramming factors induce proliferation and inhibit apoptosis of melanoma cells by changing the expression of particular genes

Wang,Yang; Sun,Hua‑Jun; Li,Rong‑Gui; Wang,Xiao‑Mei; Cheng,Zhi‑Qiang; Lou,Nan

doi:10.3892/mmr.2018.9753

Reprogramming factors induce proliferation and inhibit apoptosis of melanoma cells by changing the expression of particular genes

Authors:
- Yang Wang
- Hua‑Jun Sun
- Rong‑Gui Li
- Xiao‑Mei Wang
- Zhi‑Qiang Cheng
- Nan Lou
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Affiliations: Department of Pathology, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong 518020, P.R. China, Department of Pathology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610015, P.R. China, Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin 130012, P.R. China, Department of Orthopaedics and Traumatology, The University of Hong Kong‑Shenzhen Hospital, Shenzhen, Guangdong 518053, P.R. China
Published online on: December 12, 2018 https://doi.org/10.3892/mmr.2018.9753
Pages: 967-973
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Uncontrolled proliferation and defective apoptosis are two major factors responsible for maintaining the malignant properties of melanoma cells. Our previous study demonstrated that induced expression of four reprogramming factors remodeled the phenotype of B16‑F10 mouse melanoma cells into melanoma stem cells. The present study was conducted to investigate the effect of the four Yamanaka reprogramming factors, namely Oct4, Sox2, Klf4 and c‑Myc (OSKM), on the proliferation and apoptosis of melanoma cells, and to identify the responsible molecular signals. The results identified that expression of the four reprogramming factors was highly induced by doxycycline treatment in the stable melanoma cell clone that was transfected with a plasmid expressing these factors, driven by the Tet‑On element. It was further confirmed that induced expression of these factors enhanced the proliferation and suppressed the apoptosis of the melanoma cells. In addition, induced OSKM expression increased cell proliferation, accelerated the progression of the cell cycle, and upregulated the mRNA expression levels of Janus kinase 2 (JAK2) and Cyclin‑B1. Induced expression of these factors also decreased the apoptosis, as well as upregulated B‑cell lymphoma 2 (BCL‑2) and downregulated BCL‑2‑associated X (BAX) mRNA expression levels. Taken together, the results suggested that upregulated JAK2 and Cyclin‑B1 may be responsible for the enhanced proliferation of melanoma cells, and that BCL‑2 upregulation and BAX downregulation may account for the suppressed apoptosis of these cells.

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