Abstract
Objective
To investigate the function and mechanism of lnc NEAT1 in regulating the growth, migration and invasion of endometrial carcinoma (EC) cells.
Materials and methods
NEAT1 and miR-214-3p levels were measured by qRT-PCR. The protein levels of HMGA1, β-catenin, c-myc and MMP9 were evaluated by Western blot. The effects of NEAT1, HMGA1, miR-214-3p on the viability, migration and invasion of HEC-1A cells were accessed by WST-1 assay and transwell migration/invasion assay. The effect of miR-214-3p on Wnt signaling activity was tested by luciferase reporter assay.
Results
NEAT1, HMGA1 and β-catenin were significantly upregulated in EC tissues, and miR-214-3p was significantly downregulated. NEAT1 promoted the growth, migration and invasion of HEC-1A cells, and mRNA level of Wnt/β-catenin downstream genes c-myc and MMP9. In addition, HMGA1 upregualted the protein and mRNA levels of Wnt/β-catenin downstream genes c-myc and MMP9, and could improve cell viability, and increase numbers of migration and invasion of HEC-1A cells. miR-214-3p overexpression inhibited the proliferation, migration and invasion of HEC-1A cells, while NEAT1 overexpression reversed these effects. miR-214-3p overexpression inhibited the activity of Wnt/β-catenin pathway, while NEAT1 overexpression reversed this effect. Then, si-HMGA1 reduced the activity of Wnt/β-catenin pathway. Moreover, we found NEAT1 and HMGA1 bound to miR-214-3p by luciferase reporter assay, and NEAT1 and HMGA1 expression were negatively correlated with miR-214-3p.
Conclusion
NEAT1 regulates HMGA1 via miR-214-3p to regulate Wnt/β-catenin pathway, thus promotes the growth, migration and invasion of HEC-1A cells.
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References
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2015) Global cancer statistics. CA Cancer J Clin 65(2):87.
Chang OS, Sohn I (2014) The expression pattern of 19 genes predicts the histology of endometrial carcinoma. Sci Rep 4(6):5174
Sorosky JI (2012) Endometrial cancer. Obstet Gynecol 120(1):383–397
Kujawa KA, Lisowska KM (2015) Ovarian cancer—from biology to clinic. Postępy Higieny I Medycyny Doświadczalnej 69:1275–1290
Bartonicek N, Maag JL, Dinger ME (2016) Long noncoding RNAs in cancer: mechanisms of action and technological advancements. Mol Cancer 15(1):43
Sun C, Li S, Zhang F, Xi Y, Wang L, Bi Y, Li D (2016) Long non-coding RNA NEAT1 promotes non-small cell lung cancer progression through regulation of miR-377-3p-E2F3 pathway. Oncotarget 7(32):51784–51814
Xianguo C, Zongyao H, Jun Z, Song F, Guangyue L, Ligang Z, Kaiping Z, Yangyang Z, Chaozhao L (2016) Promoting progression and clinicopathological significance of NEAT1 over-expression in bladder cancer. Oncotarget
Li Z, Wei D, Yang C, Sun H, Lu T, Kuang D (2016) Overexpression of long noncoding RNA, NEAT1 promotes cell proliferation, invasion and migration in endometrial endometrioid adenocarcinoma. Biomed Pharmacother Biomed Pharmacother 84:244–251. doi:10.1016/j.biopha.2016.09.008
Wang Y, Zee MVD, Fodde R, Blok LJ (2010) Wnt/Β-catenin and sex hormone signaling in endometrial homeostasis and cancer. Oncotarget 1(7):674–684
Han X, Cao Y, Wang K, Zhu G (2016) HMGA1 facilitates tumor progression through regulating Wnt/β-catenin pathway in endometrial cancer. Biomed Pharmacother 82:312–318
Jurcevic S, Ejeskär K, Olsson B, Klingalevan K (2016) Verification of miRNA expression in human endometrial adenocarcinoma. BMC Cancer 16:261
Yi S-J, Li L-L, Tu W-B (2016) MiR-214 negatively regulates proliferation and WNT/β-catenin signaling in breast cancer. Eur Rev Med Pharmacol Sci 20(24):5148–5154
Derrien T, Guigó R (2010) Long non-coding RNAs with enhancer-like function in human cells. Cell 143(1):46–58
Geisler S, Lojek L, Khalil A, Baker K, Coller J (2012) Decapping of long noncoding RNAs regulates inducible genes. Mol Cell 45(3):279
Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL (2010) Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464(7291):1071–1076
Nie FQ, Zhu Q, Xu TP, Zou YF, Xie M, Sun M, Xia R, Lu KH (2014) Long non-coding RNA MVIH indicates a poor prognosis for non-small cell lung cancer and promotes cell proliferation and invasion. Tumor Biol 35(8):7587–7594
Pan LJ, Zhong TF, Tang RX, Li P, Dang YW, Huang SN, Chen G (2015) Upregulation and clinicopathological significance of long non-coding NEAT1 RNA in NSCLC tissues. Asian Pac J Cancer Prev Apjcp 16(7):2851–2855
Peng W, Wu T, Han Z, Jin Q, He G, Yu H, Xuan L, Xin W, Tian L, Sun Y (2016) Long noncoding RNA NEAT1 promotes laryngeal squamous cell cancer through regulating miR-107/CDK6 pathway. J Exp Clin Cancer Res 35(1):22
Chai Y, Liu J, Zhang Z, Liu L (2016) HuR-regulated lncRNA NEAT1 stability in tumorigenesis and progression of ovarian cancer. Cancer Med (Baltim) 5(7):1588–1598
Smolle MA, Bullock MD, Hui L, Martin P, Johannes H (2015) Long non-coding RNAs in endometrial carcinoma. Int J Mol Sci 16(11):26463–26472
Akrami R, Jacobsen A, Hoell J, Schultz N, Sander C, Larsson E (2013) Comprehensive analysis of long non-coding RNAs in ovarian cancer reveals global patterns and targeted DNA amplification. PLoS One 8(11):e80306
He X, Bao W, Li X, Chen Z, Che Q, Wang H, Wan XP (2014) The long non-coding RNA HOTAIR is upregulated in endometrial carcinoma and correlates with poor prognosis. Int J Mol Med 33(2):325
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JW performed the experiments and XZ analyzed the data. ZG and XM contributed to the quality control of data and algorithms. YS wrote the manuscript. YG conceived and designed the experiments and analyzed the data. All authors read and approved the final manuscript.
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Wang, J., Zhao, X., Guo, Z. et al. Regulation of NEAT1/miR-214-3p on the growth, migration and invasion of endometrial carcinoma cells. Arch Gynecol Obstet 295, 1469–1475 (2017). https://doi.org/10.1007/s00404-017-4365-1
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DOI: https://doi.org/10.1007/s00404-017-4365-1