Abstract
This study aimed to characterize the expression status and potentially mechanistic involvement of SNHG7 in pituitary adenoma. Relative expression of SNHG7 and miR-449a was analyzed by real-time PCR. Cell viability was measured with Cell Counting Kit-8 (CCK-8). Cell apoptosis was determined by PI/Annexin V double staining followed by flow cytometry analysis. Cell invasion and migration were analyzed by wound healing and transwell assays, respectively. The regulatory action of miR-449a on SNHG7 was interrogated by luciferase reporter assay. We also investigated the pro-tumor activity of SNHG7 with the MMQ xenograft tumor mouse model. We identified the aberrant up-regulation of SNHG7 in pituitary adenoma both in vivo and in vitro, which associated with poor survival outcome. siRNA-mediated SNHG7-knockdown decreased cell viability, increased apoptosis and compromised migration and invasion. We further predicted and validated that SNHG7 negatively regulated miR-449a via sponging. Concurrent inhibition of miR-449a restored cell viability, apoptosis, migration and invasion influenced by SNHG7-deficiency. Most importantly, we demonstrated that SNHG7-silencing delayed xenograft tumor progression, which was accompanied with increased miR-449a and decreased Ki67 intensity. Our study highlighted the essential oncogenic properties of the SNHG7/miR-449a axis in pituitary adenoma.
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References
Bou Kheir T, Futoma-Kazmierczak E, Jacobsen A, Krogh A, Bardram L, Hother C, Grønbæk K, Federspiel B, Lund AH, Friis-Hansen L (2011) miR-449 inhibits cell proliferation and is down-regulated in gastric cancer. Mol Cancer 10:29. https://doi.org/10.1186/1476-4598-10-29
Buurman R, Gürlevik E, Schäffer V, Eilers M, Sandbothe M, Kreipe H, Wilkens L, Schlegelberger B, Kühnel F, Skawran B (2012) Histone deacetylases activate hepatocyte growth factor signaling by repressing microRNA-449 in hepatocellular carcinoma cells. Gastroenterology 143:811–820 e815. https://doi.org/10.1053/j.gastro.2012.05.033
Chanson P, Raverot G, Castinetti F, Cortet-Rudelli C, Galland F, Salenave S, French Endocrinology Society non-functioning pituitary adenoma w-g (2015) Management of clinically non-functioning pituitary adenoma. Ann Endocrinol (Paris) 76:239–247. https://doi.org/10.1016/j.ando.2015.04.002
Chen Y, Peng Y, Xu Z, Ge B, Xiang X, Zhang T, Gao L, Shi H, Wang C, Huang J (2019) Knockdown of lncRNA SNHG7 inhibited cell proliferation and migration in bladder cancer through activating Wnt/beta-catenin pathway. Pathol Res Pract 215:302–307. https://doi.org/10.1016/j.prp.2018.11.015
Ezzat S, Asa SL, Couldwell WT, Barr CE, Dodge WE, Vance ML, IE MC (2004) The prevalence of pituitary adenomas: a systematic review. Cancer 101:613–619. https://doi.org/10.1002/cncr.20412
Fang Y, Gu X, Li Z, Xiang J, Chen Z (2013) miR-449b inhibits the proliferation of SW1116 colon cancer stem cells through downregulation of CCND1 and E2F3 expression. Oncol Rep 30:399–406. https://doi.org/10.3892/or.2013.2465
Han Y, Hu H, Zhou J (2019) Knockdown of LncRNA SNHG7 inhibited epithelial-mesenchymal transition in prostate cancer though miR-324-3p/WNT2B axis in vitro. Pathol Res Pract 215:152537. https://doi.org/10.1016/j.prp.2019.152537
Huang S, Zheng S, Huang S, Cheng H, Lin Y, Wen Y, Lin W (2019) Flot2 targeted by miR-449 acts as a prognostic biomarker in glioma. Artif Cells Nanomed Biotechnol 47:250–255. https://doi.org/10.1080/21691401.2018.1549062
Jang SG, Yoo CW, Park SY, Kang S, Kim HK (2014) Low expression of miR-449 in gynecologic clear cell carcinoma. Int J Gynecol Cancer 24:1558–1563. https://doi.org/10.1097/IGC.0000000000000267
Jiang J, Yang X, He X, Ma W, Wang J, Zhou Q, Li M, Yu S (2019) MicroRNA-449b-5p suppresses the growth and invasion of breast cancer cells via inhibiting CREPT-mediated Wnt/beta-catenin signaling. Chem Biol Interact 302:74–82. https://doi.org/10.1016/j.cbi.2019.02.004
Kapranov P, Cheng J, Dike S, Nix DA, Duttagupta R, Willingham AT, Stadler PF, Hertel J, Hackermuller J, Hofacker IL, Bell I, Cheung E, Drenkow J, Dumais E, Patel S, Helt G, Ganesh M, Ghosh S, Piccolboni A, Sementchenko V, Tammana H, Gingeras TR (2007) RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science 316:1484–1488. https://doi.org/10.1126/science.1138341
Li LP, Wu WJ, Sun DY, Xie ZY, Ma YC, Zhao YG (2014) miR-449a and CDK6 in gastric carcinoma. Oncol Lett 8:1533–1538. https://doi.org/10.3892/ol.2014.2370
Li Z, Huang X, Xu J, Su Q, Zhao J, Ma J (2016) miR-449 overexpression inhibits papillary thyroid carcinoma cell growth by targeting RET kinase-beta-catenin signaling pathway. Int J Oncol 49:1629–1637. https://doi.org/10.3892/ijo.2016.3659
Lin P, Liu X, Wang S, Li X, Song Y, Li L, Cai S, Wang X, Chen J (2018) Diagnosing pituitary adenoma in unstained sections based on multiphoton microscopy. Pituitary 21:362–370. https://doi.org/10.1007/s11102-018-0882-6
Luo W, Huang B, Li Z, Li H, Sun L, Zhang Q, Qiu X, Wang E (2013) MicroRNA-449a is downregulated in non-small cell lung cancer and inhibits migration and invasion by targeting c-Met. PLoS One 8:e64759. https://doi.org/10.1371/journal.pone.0064759
McCarthy PM, Piehler JM, Schaff HV, Pluth JR, Orszulak TA, Vidaillet HJ Jr, Carney JA (1986) The significance of multiple, recurrent, and "complex" cardiac myxomas. J Thorac Cardiovasc Surg 91:389–396
Newey PJ, Thakker RV (2011) Role of multiple endocrine neoplasia type 1 mutational analysis in clinical practice. Endocr Pract 17(Suppl 3):8–17. https://doi.org/10.4158/EP10379.RA
Qi H, Wen B, Wu Q, Cheng W, Lou J, Wei J, Huang J, Yao X, Weng G (2018) Long noncoding RNA SNHG7 accelerates prostate cancer proliferation and cycle progression through cyclin D1 by sponging miR-503. Biomed Pharmacother 102:326–332. https://doi.org/10.1016/j.biopha.2018.03.011
Qu L, Ding J, Chen C, Wu ZJ, Liu B, Gao Y, Chen W, Liu F, Sun W, Li XF, Wang X, Wang Y, Xu ZY, Gao L, Yang Q, Xu B, Li YM, Fang ZY, Xu ZP, Bao Y, Wu DS, Miao X, Sun HY, Sun YH, Wang HY, Wang LH (2016) Exosome-transmitted lncARSR promotes sunitinib resistance in renal cancer by acting as a competing endogenous RNA. Cancer Cell 29:653–668. https://doi.org/10.1016/j.ccell.2016.03.004
Ransohoff JD, Wei Y, Khavari PA (2018) The functions and unique features of long intergenic non-coding RNA. Nat Rev Mol Cell Biol 19:143–157. https://doi.org/10.1038/nrm.2017.104
Sun X, Huang T, Liu Z, Sun M, Luo S (2019) LncRNA SNHG7 contributes to tumorigenesis and progression in breast cancer by interacting with miR-34a through EMT initiation and the Notch-1 pathway. Eur J Pharmacol 856:172407. https://doi.org/10.1016/j.ejphar.2019.172407
Wang C, Tan C, Wen Y, Zhang D, Li G, Chang L, Su J, Wang X (2019) FOXP1-induced lncRNA CLRN1-AS1 acts as a tumor suppressor in pituitary prolactinoma by repressing the autophagy via inactivating Wnt/beta-catenin signaling pathway. Cell Death Dis 10:499. https://doi.org/10.1038/s41419-019-1694-y
Wu ZR, Yan L, Liu YT, Cao L, Guo YH, Zhang Y, Yao H, Cai L, Shang HB, Rui WW, Yang G, Zhang XB, Tang H, Wang Y, Huang JY, Wei YX, Zhao WG, Su B, Wu ZB (2018) Inhibition of mTORC1 by lncRNA H19 via disrupting 4E-BP1/raptor interaction in pituitary tumours. Nat Commun 9:4624. https://doi.org/10.1038/s41467-018-06853-3
Zhang H, Feng Z, Huang R, Xia Z, Xiang G, Zhang J (2014) MicroRNA-449 suppresses proliferation of hepatoma cell lines through blockade lipid metabolic pathway related to SIRT1. Int J Oncol 45:2143–2152. https://doi.org/10.3892/ijo.2014.2596
Zhang Z, Wang J, Gao R, Yang X, Zhang Y, Li J, Zhang J, Zhao X, Xi C, Lu X (2017) Downregulation of microRNA-449 promotes migration and invasion of breast cancer cells by targeting tumor protein D52 (TPD52). Oncol Res 25:753–761. https://doi.org/10.3727/096504016X14772342320617
Zhang Y, Yuan Y, Zhang Y, Cheng L, Zhou X, Chen K (2020) SNHG7 accelerates cell migration and invasion through regulating miR-34a-Snail-EMT axis in gastric cancer. Cell Cycle 19:142–152. https://doi.org/10.1080/15384101.2019.1699753
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All authors participated in the design, interpretation of the studies and analysis of the data and review of the manuscript; Xiongfei Yue, Ce Dong, Zhanying Ye, Lin Zhu, Xiaoyang Zhang, Xiaoyan Wang, Feng Mo, Zheng Li, Baogen Pan conducted the experiments, Baogen Pan wrote the manuscript.
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The animal study was approved by the Institutional Animal Care and Use Committee of Hebei General Hospital.
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Yue, X., Dong, C., Ye, Z. et al. LncRNA SNHG7 sponges miR-449a to promote pituitary adenomas progression. Metab Brain Dis 36, 123–132 (2021). https://doi.org/10.1007/s11011-020-00611-5
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DOI: https://doi.org/10.1007/s11011-020-00611-5