The role of dosage-sensitive sex reversal-adrenal hypoplasia congenita region on the X chromosome 1 in autophagy and proliferation on pituitary adenoma cells
CHEN Xianbin1, HU Qiongshuang1, LYU Fangfang2, LU Jianglong1, LI Qun1
1.Department of Neurosurgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China; 2.Department of Children’s Respiratory Disease, the Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China
CHEN Xianbin,HU Qiongshuang,LYU Fangfang, et al. The role of dosage-sensitive sex reversal-adrenal hypoplasia congenita region on the X chromosome 1 in autophagy and proliferation on pituitary adenoma cells[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2022, 52(6): 459-464,471.
Objective: To investigate the role of the dosage-sensitive sex reversal-adrenal hypoplasia congenita region on the X chromosome 1 (DAX-1) in autophagy and proliferation of pituitary tumor cells. Methods: The differential gene group between pituitary tumors and normal pituitaries was screened by Microarray and the expression difference of DAX-1 between invasive pituitary tumor and non-invasive pituitary tumor was analyzed by Pubmed database. The expression of DAX-1 pair was knocked down by small interfering RNAs (siRNA), and the effect of DAX-1 on MMQ cells proliferation was detected by CCK-8 and colony formation assays. The expression of autophagy related genes ATG5, ATG7 and ATG12 was detected by real-time quantitative polymerase chain reaction (RT-qPCR). Western blot and immunofluorescence experiments were performed to detect the effect of DAX-1 on the expression of LC3. Finally, xenograft experiments in nude mice was made to
observe the effect of DAX-1 knockdown on the growth and autophagy of pituitary tumor cells. Results: Compared with normal pituitary tumors, the DAX-1 gene expression was significantly down-regulated in pituitary tumors,and was lower in invasive and non-invasive pituitary tumors (P<0.05). Knockdown DAX-1 could promote MMQ cells proliferation, while overexpression of DAX-1 inhibited proliferation of MMQ cells and promoted drug sensitivity of cabergoline and bromocriptine (P<0.05). In addition, knocking-down DAX-1 could inhibit the autophagy level in MMQ cells. It was proved that knocking down DAX-1 promoted tumor growth in vivo (P<0.05). Conclusion: The DAX-1 expression is decreased in pituitary tumors, and the decreased DAX-1 promotes the development of pituitary tumors. DAX-1 may be a potential therapeutic target for pituitary tumors.