机构:[1]Institute of Neuroscience, Kunming Medical University, Kunming, China[2]Department of Neurosurgery, 1st Affiliated Hospital of Kunming MedicalUniversity, Kunming, China[3]Yunnan Key Laboratory of Laboratory Medicine,Yunnan Engineering Technology Center of Digestive disease, 1st AffiliatedHospital of Kunming Medical University, Kunming, China昆明医科大学附属第一医院[4]Genetic DiagnosisCenter, Women and Children Hospital, Kunming, China[5]Department ofNeurosurgery, Affiliated Hospital of Hubei University of Medicine, Xiangyang,China[6]Department of Neurosurgery, The People’s Hospital of Chuxiong,Chuxiong, China[7]Biomedical Engineering Research Center, Kunming MedicalUniversity, Kunming, China
Long noncoding RNAs (lncRNAs) and their crosstalks with other RNAs have been revealed to be closely related to tumorigenesis and development, but their role in invasive pituitary adenoma (IPA) remains largely unclear. In our study, LINC00473 was identified as the most upregulated lncRNA in IPA by whole transcriptome RNA sequencing (RNA-Seq). Further, its related signaling pathway LINC00473/miR-502-3p/KMT5A was obtained by constructing a competing endogenous RNA (ceRNA) regulatory network. Their expression in IPA and non-invasive pituitary adenoma (NIPA) tissues was verified by qRT-PCR. Then the effects and mechanisms of LINC00473 and its ceRNA network on the proliferation of pituitary adenoma (PA) cells were confirmed by gene overexpression or silencing techniques combined with CCK-8 assay, EdU staining, flow cytometry assay, and double luciferase reporter gene assay in PA cell lines AtT-20 and GT1-1 in vitro and in a xenograft model in vivo. LINC00473 is overexpressed in IPA and can promote PA cells proliferation. Mechanistically, overexpression of LINC00473 restricts miR-502-3p through the ceRNA mechanism, upregulates KMT5A expression, and promotes the expression of cyclin D1 and CDK2, which is conducive to the cell cycle process, thereby promoting the proliferation of PA cells, involving IPA progression.
基金:
Health Scientific Foundation of Yunnan ProvinceNatural Science Foundation of Yunnan Province [2016NS057]; Applied Basic Research Foundation of Yunnan Province [201601CH00139]; Research Innovation Team of Yunnan Province [2019HC022]; Medical Academic Leader Training Program of Yunnan Province [D201618]; Doctorate Innovation Foundation of Kunming Medical University [2019D001]; Outstanding Youth Scientists and Technicians Training Program of Yunnan Province
第一作者机构:[1]Institute of Neuroscience, Kunming Medical University, Kunming, China[2]Department of Neurosurgery, 1st Affiliated Hospital of Kunming MedicalUniversity, Kunming, China
通讯作者:
推荐引用方式(GB/T 7714):
Li Junjun,Qian Yuan,Zhang Chao,et al.LncRNA LINC00473 is involved in the progression of invasive pituitary adenoma by upregulating KMT5A via ceRNA-mediated miR-502-3p evasion[J].CELL DEATH & DISEASE.2021,12(6):doi:10.1038/s41419-021-03861-y.
APA:
Li, Junjun,Qian, Yuan,Zhang, Chao,Wang, Wei,Qiao, Yisheng...&Deng, Xingli.(2021).LncRNA LINC00473 is involved in the progression of invasive pituitary adenoma by upregulating KMT5A via ceRNA-mediated miR-502-3p evasion.CELL DEATH & DISEASE,12,(6)
MLA:
Li, Junjun,et al."LncRNA LINC00473 is involved in the progression of invasive pituitary adenoma by upregulating KMT5A via ceRNA-mediated miR-502-3p evasion".CELL DEATH & DISEASE 12..6(2021)