title: Hypoxia-responsive miR-124 and miR-144 reduce hypoxia-induced autophagy and enhance radiosensitivity of prostate cancer cells via suppressing PIM1.
abstract: Cancer cells in hypoxia usually make adaptive changes in cellular metabolism, such as altered autophagy. This might be a cause of enhanced radioresistance in some types of cancer. In this study, we investigated hypoxia-responsive miRNAs in two prostate cancer cell lines (DU145 and PC3). This study firstly reported that hypoxia induces further downregulation of miR-124 and miR-144, which might be a result of impaired dicer expression. These two miRNAs can simultaneously target 3'UTR of PIM1. Functional study showed that miR-124 or miR-144 overexpression can inhibit hypoxia-induced autophagy and enhance radiosensitivity at least via downregulating PIM1. Therefore, hypoxia induced miR-124 and miR-144 downregulation may contribute to a prosurvival mechanism of prostate cancer cells to hypoxia and irradiation at least through attenuated suppressing of PIM1. This finding presents a potential therapeutic target for prostate cancer.
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Henan, 450052, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Gu
authors.affiliation: Department of Traditional Chinese Medicine, The First Affiliated Hospital of Zhengzhou University, Henan, 450052, China.
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Henan, 450052, China.
authors.forename: Changmao
authors.initials: C
authors.lastname: Ding
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Henan, 450052, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Henan, 450052, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Nuclear Medicine, Henan Provincial People's Hospital & the People's Hospital of Zhengzhou University, Henan, 450003, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Henan, 450052, China.
authors.forename: Ruitai
authors.initials: R
authors.lastname: Fan
mesh_terms: D020413:3' Untranslated Regions; D001343:Autophagy / Q000235:genetics*; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000860:Hypoxia / Q000235:genetics* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D051573:Proto-Oncogene Proteins c-pim-1 / Q000737:chemistry / Q000235:genetics*; D034622:RNA Interference; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics*; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C509207:MIRN124 microRNA, human; C554293:MIRN144 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C496634:PIM1 protein, human; D051573:Proto-Oncogene Proteins c-pim-1; D043244:Ribonuclease III
keywords: Autophagy; PIM1; hypoxia; miR-124; miR-144; radiosensitivity