miR-204 reverses temozolomide resistance and inhibits cancer initiating cells phenotypes by degrading FAP-α in glioblastoma

Yang,Yun‑Na; Zhang,Xiang‑Hua; Wang,Yan‑Ming; Zhang,Xi; Gu,Zheng

doi:10.3892/ol.2018.8301

miR-204 reverses temozolomide resistance and inhibits cancer initiating cells phenotypes by degrading FAP-α in glioblastoma

Authors:
- Yun‑Na Yang
- Xiang‑Hua Zhang
- Yan‑Ming Wang
- Xi Zhang
- Zheng Gu
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Affiliations: Department of Neurosurgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100043, P.R. China, Department of Neurosurgery, Beijing Friendship Hospital affiliated to Capital Medical University, Beijing 100050, P.R. China, Department of Spinal Surgery, Dezhou People's Hospital, Dezhou, Shandong 25301, P.R. China, Department of Pharmacy, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100043, P.R. China
Published online on: March 20, 2018 https://doi.org/10.3892/ol.2018.8301
Pages: 7563-7570
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Malignant gliomas are treated with temozolomide (TMZ) at present, but often exhibit resistance to this agent. Cancer-initiating cells (CICs) have been suggested to lead to TMZ resistance. The mechanisms underlying CICs‑based TMZ resistance are not fully understood. MicroRNAs (miRNAs) have been demonstrated to serve important roles in tumorigenesis and TMZ resistance. In the present study, a sphere forming assay and western blot analysis were performed to detect the formation of CICs and fibroblast activation protein α (FAP‑α) protein expression. It was revealed that TMZ resistance promoted the formation of CICs and upregulated FAP‑α expression in glioblastoma cells. Over‑expressing FAP‑α was also demonstrated to promote TMZ resistance and induce the formation of CICs in U251MG cells. In addition, using a reverse transcription‑quantitative polymerase chain reaction, it was observed that miR‑204 was downregulated in U251MG‑resistant (‑R) cells. miR‑204 expression negatively correlated with the FAP‑α levels in human glioblastoma tissues, and it may inhibit the formation of CICs and reverse TMZ resistance in U251MG‑R cells. Therefore, it was concluded that miR‑204 reversed temozolomide resistance and inhibited CICs phenotypes by degrading FAP-α in glioblastoma.

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