{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T06:41:31Z","timestamp":1762324891682,"version":"3.41.2"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,12,9]],"date-time":"2020-12-09T00:00:00Z","timestamp":1607472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870964"],"award-info":[{"award-number":["81870964"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LY17H090012, Q17H090013"],"award-info":[{"award-number":["LY17H090012, Q17H090013"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Nonfunctioning pituitary neuroendocrine tumor (NF-PitNET) is difficult to resect. Except for surgery, there is no effective treatment for NF-PitNET. MicroRNA-134 (miR-134) has been reported to inhibit proliferation and invasion ability of tumor cells. Herein, the mechanism underlying the effect of miR-134 on alleviating NF-PitNET tumor cells growth is explored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mouse pituitary \u03b1T3-1 cells were transfected with miR-134 mimics and inhibitor, followed by treatment with stromal cell-derived factor-1\u03b1 (SDF-1\u03b1) <jats:italic>in vitro<\/jats:italic>. MiR-134 expression level: we used quantitative real-time PCR (qRT-PCR) to detect the expression of miR-134. Cell behavior level: cell viability and invasion ability were assessed using a cell counting kit-8 (CCK8) assay and Transwell invasion assay respectively. Cytomolecular level: tumor cell proliferation was evaluated by Ki-67 staining; propidium iodide (PI) staining analyzed the effect of miR-134 on cell cycle arrest; western blot analysis and immunofluorescence staining evaluated tumor migration and invasive ability. Additionally, we collected 27 NF-PitNET tumor specimens and related clinical data. The specimens were subjected to qRT-PCR to obtain the relative miR-134 expression level of each specimen; linear regression analysis was used to analyze the miR-134 expression level in tumor specimens and the age of the NF-PitNET population, gender, tumor invasion, prognosis, and other indicators.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>In vitro<\/jats:italic> experiment, miR-134 was observed to significantly inhibit \u03b1T3-1 cells proliferation characterized by inhibited cell viability and expressions of vascular endothelial growth factor A (VEGFA) and cell cycle transition from G1 to S phase (<jats:italic>P<\/jats:italic> &amp;lt; 0.01). VEGFA was verified as a target of miR-134. Additionally, miR-134-induced inhibition of \u03b1T3-1 cell proliferation and invasion was attenuated by SDF-1\u03b1 and VEGFA overexpression (<jats:italic>P<\/jats:italic> &amp;lt; 0.01). In primary NF-PitNET tumor analysis, miR-134 expression level was negatively correlated with tumor invasion (<jats:italic>P = 0.003<\/jats:italic>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The regulation of the SDF-1\u03b1\/miR-134\/VEGFA axis represents a novel mechanism in the pathogenesis of NF-PitNETs and may serve as a potential therapeutic target for the treatment of NF-PitNETs.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2020.566761","type":"journal-article","created":{"date-parts":[[2020,12,9]],"date-time":"2020-12-09T20:16:00Z","timestamp":1607544960000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["SDF-1\u03b1\/MicroRNA-134 Axis Regulates Nonfunctioning Pituitary Neuroendocrine Tumor Growth via Targeting VEGFA"],"prefix":"10.3389","volume":"11","author":[{"given":"Xiaoyu","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanjian","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunxiang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoming","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenguang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianmin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Hong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2020,12,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jocn.2017.01.015","article-title":"The impact of transsphenoidal surgery on neurocognitive function: A systematic review","volume":"42","author":"Alsumali","year":"2017","journal-title":"J Clin Neurosci"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2009.05.005","article-title":"Non-functioning pituitary adenomas","volume":"23","author":"Greenman","year":"2009","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-018-1570-z","article-title":"Complete evaluation of pituitary tumours in a single tertiary care institution","volume":"60","author":"Askitis","year":"2018","journal-title":"Endocrine"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2015.151","article-title":"Silent subtype 3 pituitary adenomas are not always silent and represent poorly differentiated monomorphous plurihormonal Pit-1 lineage adenomas","volume":"29","author":"Mete","year":"2016","journal-title":"Mod Pathol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"C5","DOI":"10.1530\/erc-17-0004","article-title":"From pituitary adenoma to pituitary neuroendocrine tumor (PitNET): an International Pituitary Pathology Club proposal","volume":"24","author":"Asa","year":"2017","journal-title":"Endocr Relat Cancer"},{"key":"B6","doi-asserted-by":"publisher","first-page":"R113","DOI":"10.1530\/eje-17-0216","article-title":"MANAGEMENT OF ENDOCRINE DISEASE: Present and future perspectives for medical therapy of nonfunctioning pituitary adenomas","volume":"177","author":"Greenman","year":"2017","journal-title":"Eur J Endocrinol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.endonu.2013.04.009","article-title":"Non-functioning pituitary tumors: 2012 update","volume":"61","author":"C\u00e1mara G\u00f3mez","year":"2014","journal-title":"Endocrinol Nutr"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-015-0685-8","article-title":"Optimal management of non-functioning pituitary adenomas","volume":"50","author":"Greenman","year":"2015","journal-title":"Endocrine"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00546.2011","article-title":"MicroRNA miR-107 is overexpressed in pituitary adenomas and inhibits the expression of aryl hydrocarbon receptor-interacting protein in vitro","volume":"303","author":"Trivellin","year":"2012","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.07.002","article-title":"Silencing of the imprinted DLK1-MEG3 locus in human clinically nonfunctioning pituitary adenomas","volume":"179","author":"Cheunsuchon","year":"2011","journal-title":"Am J Pathol"},{"key":"B11","article-title":"Subclinical adenomas of the human pituitary. 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