MiR-223/PAX6 Axis Regulates Glioblastoma Stem Cell Proliferation and the Chemo Resistance to TMZ via Regulating PI3K/Akt Pathway.
Chemotherapy is a standard strategy for glioma, while chemoresistance remains a major therapeutic challenge in current clinical practice. Our present study was aimed to determine whether inhibition of the miR-223/paired box 6 (PAX6) pathway could increase the sensitivity of glioma to Temozolomide. An elevated level of miR-223 was observed in glioma tissues. Exogenous miR-223 promoted cell survival when exposed to Temozolomide (TMZ), while miR-223 inhibition could reverse this process. The RNA and protein levels of PAX6 were significantly decreased by exogenous miR-223, and the 3'-untranslated region of PAX6 was shown to be a target of miR-223. Besides, it has also been reported that PI3K/Akt signaling pathway is pivotal to regulate glioma growth and proliferation. In the present study, we revealed that miR-223/PAX6 axis regulated the growth, invasion, and chemo resistance of glioblastoma stem cells to TMZ via regulating PI3K/Akt signaling pathway, which present a novel potential therapy for intervention of glioblastoma. Taken together, our findings shed new light on the miR-223/PAX6 pathway in glioma and this pathway might modulate the sensitivity of glioma to TMZ via regulating PI3K/Akt signaling pathway. J. Cell. Biochem. 118: 3452-3461, 2017. © 2017 Wiley Periodicals, Inc.
Department of Physiology, School of Basic Medical Science, Central South University, Changsha 410008, P. R. China.
Bai-Sheng
0000-0001-7293-277X
BS
Huang
Department of Immunology, School of Basic Medical Science, Central South University, Changsha 410008, P. R. China.
Qi-Zhi
QZ
Luo
Department of Physiology, School of Basic Medical Science, Central South University, Changsha 410008, P. R. China.
Yang
Y
Han
Department of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha 410013, P. R. China.
Dong
D
Huang
Department of Rehabilitation, Brain Hospital of Hunan Province, Hunan University of Chinese Medicine, Changsha 410007, P. R. China.
Qing-Ping
QP
Tang
Department of Physiology, School of Basic Medical Science, Central South University, Changsha 410008, P. R. China.
Li-Xiang
LX
Wu
D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D000071841:PAX6 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D000077204:Temozolomide
D003606:Dacarbazine; D035683:MicroRNAs; D000071841:PAX6 Transcription Factor; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D012334:RNA, Neoplasm; D000077204:Temozolomide; C525067:MIR223, human; C000605730:PAX6 protein, human
CHEMORESISTANCE; GLIOMA; PAIRED BOX 6 (PAX6); TEMOZOLOMIDE (TMZ); miR-223