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Construction of lncRNA regulatory networks reveal the key lncRNAs associated with Pituitary adenomas progression

  • Received: 20 May 2019 Accepted: 28 November 2019 Published: 06 January 2020
  • Pituitary adenomas (PA) is one of the most frequent types of intracranial neoplasms. Long noncoding RNAs (lncRNAs) played important roles in the progression of human cancers, including PA. However, the roles of lncRNAs in PA remained to be further investigated. We performed analysis of GSE26966 dataset to identify differently expressed lncRNAs in PA. Co-expression network, lncRNA-RNA binding proteins network, and competing endogenous RNA networks were constructed. Moreover, we performed RT-qPCR assay to validate four key lncRNAs expression in PA. This study identified differently expressed mRNAs and lncRNAs by using GSE26966 database. Furthermore, we constructed lncRNA-mRNA co-expression, lncRNA-RBP interaction and ceRNA networks. Bioinformatics analysis showed these lncRNAs were involved in regulating mechanical stimulus, gene expression, JAK-STAT cascade, cell cycle arrest, FoxO signaling, HIF-1 signaling, Insulin signaling, Oxytocin signaling, and MAPK signaling. We also showed KCNQ1OT1, SNHG7, MEG3, and SNHG5 were down-regulated in PA. Our findings could provide a novel insight to understand the mechanisms of lncRNAs underlying PA pathogenesis and identify new biomarkers for PA.

    Citation: Yonghua Xue, Yiqin Ge. Construction of lncRNA regulatory networks reveal the key lncRNAs associated with Pituitary adenomas progression[J]. Mathematical Biosciences and Engineering, 2020, 17(3): 2138-2149. doi: 10.3934/mbe.2020113

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  • Pituitary adenomas (PA) is one of the most frequent types of intracranial neoplasms. Long noncoding RNAs (lncRNAs) played important roles in the progression of human cancers, including PA. However, the roles of lncRNAs in PA remained to be further investigated. We performed analysis of GSE26966 dataset to identify differently expressed lncRNAs in PA. Co-expression network, lncRNA-RNA binding proteins network, and competing endogenous RNA networks were constructed. Moreover, we performed RT-qPCR assay to validate four key lncRNAs expression in PA. This study identified differently expressed mRNAs and lncRNAs by using GSE26966 database. Furthermore, we constructed lncRNA-mRNA co-expression, lncRNA-RBP interaction and ceRNA networks. Bioinformatics analysis showed these lncRNAs were involved in regulating mechanical stimulus, gene expression, JAK-STAT cascade, cell cycle arrest, FoxO signaling, HIF-1 signaling, Insulin signaling, Oxytocin signaling, and MAPK signaling. We also showed KCNQ1OT1, SNHG7, MEG3, and SNHG5 were down-regulated in PA. Our findings could provide a novel insight to understand the mechanisms of lncRNAs underlying PA pathogenesis and identify new biomarkers for PA.


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    [1] L. Koch, Functional genomics: Screening for lncRNA function, Nat. Rev. Genet., 18 (2017), 70.
    [2] E. Lau, Non-coding RNA: Zooming in on lncRNA functions, Nat. Rev. Genet., 15 (2014), 574-575.
    [3] G. St Laurent, C. Wahlestedt, P. Kapranov, The Landscape of long noncoding RNA classification, Trends Genet., 31 (2015), 239-251.
    [4] Y. Zhao, Q. Guo, J. Chen, J. Hu, S. Wang, Y. Sun, Role of long non-coding RNA HULC in cell proliferation, apoptosis and tumor metastasis of gastric cancer: A clinical and in vitro investigation, Oncol. Rep., 31 (2014), 358-364.
    [5] L. Ying, Y. Huang, H. Chen, Y. Wang, L. Xia, Y. Chen, et al., Downregulated MEG3 activates autophagy and increases cell proliferation in bladder cancer, Mol. Biosyst., 9 (2013), 407-411.
    [6] J. T. Lee, Epigenetic regulation by long noncoding RNAs, Science, 338 (2012), 1435-1439.
    [7] K. C. Wang, H. Y. Chang, Molecular mechanisms of long noncoding RNAs, Mol. Cell, 43 (2011), 904-914.
    [8] F. Russo, G. Fiscon, F. Conte, M. Rizzo, P. Paci, M. Pellegrini, Interplay Between Long Noncoding RNAs and MicroRNAs in Cancer, in Computation Cell Biology, Humana Press, New York, (2018), 75-92.
    [9] Y. Y. Qian, K. Li, Q. Y. Liu, Z. S. Liu, Long non-coding RNA PTENP1 interacts with miR-193a-3p to suppress cell migration and invasion through the PTEN pathway in hepatocellular carcinoma, Oncotarget, 8 (2017), 107859-107869.
    [10] R. Zhang, Y. Guo, Z. Ma, G. Ma, Q. Xue, F. Li, et al., Long non-coding RNA PTENP1 functions as a ceRNA to modulate PTEN level by decoying miR-106b and miR-93 in gastric cancer, Oncotarget, 8 (2017), 26079-26089.
    [11] L. Yang, C. Lin, C. Jin, J. C. Yang, B. Tanasa, W. Li, et al., lncRNA-dependent mechanisms of androgen-receptor-regulated gene activation programs, Nature, 500 (2013), 598-602.
    [12] S. Melmed, Pathogenesis of pituitary tumors, Nat. Rev. Endocrinol., 7 (2011), 257-266.
    [13] B. M. Arafah, M. P. Nasrallah, Pituitary tumors: Pathophysiology, clinical manifestations and management, Endocr. Relat. Cancer, 8 (2001), 287-305.
    [14] H. Fukuoka, O. Cooper, A. Ben-Shlomo, A. Mamelak, S. G. Ren, D. Bruyette, et al., EGFR as a therapeutic target for human, canine, and mouse ACTH-secreting pituitary adenomas, J. Clin. Invest., 121 (2012), 4712-4721.
    [15] J. Wang, B. Voellger, J. Benzel, U. Schlomann, C. Nimsky, J. W. Bartsch, Metalloproteinases ADAM12 and MMP-14 are associated with cavernous sinus invasion in pituitary adenomas, Int. J. Cancer, 139 (2016), 1327-1339.
    [16] V. Leone, C. Langella, D. D'Angelo, P. Mussnich, A. Wierinckx, L. Terracciano, et al., Mir-23b and miR-130b expression is downregulated in pituitary adenomas, Mol. Cell. Endocrinol., 390 (2014), 1-7.
    [17] E. Gentilin, F. Tagliati, C. Filieri, D. Mole, M. Minoia, M. R. Ambrosio, et al., miR-26a plays an important role in cell cycle regulation in ACTH-secreting pituitary adenomas by modulating protein kinase Cdelta, Endocrinology, 154 (2013), 1690-1700.
    [18] G. Lu, J. Duan, D. Zhou, Long-noncoding RNA IFNG-AS1 exerts oncogenic properties by interacting with epithelial splicing regulatory protein 2 (ESRP2) in pituitary adenomas, Pathol. Res. Pract., 214 (2018), 2054-2061.
    [19] H. Wang, G. Wang, Y. Gao, C. Zhao, X. Li, F. Zhang, Lnc-SNHG1 Activates the TGFBR2/SMAD3 and RAB11A/Wnt/beta-Catenin Pathway by Sponging MiR-302/372/373/520 in Invasive Pituitary Tumors, Cell. Physiol. Biochem., 48 (2018), 1291-1303.
    [20] P. Chunharojrith, Y. Nakayama, X. Jiang, R. E. Kery, J. Ma, C. S. De La Hoz Ulloa, et al., Tumor suppression by MEG3 lncRNA in a human pituitary tumor derived cell line, Mol. Cell. Endocrinol., 416 (2015), 27-35. doi: 10.1016/j.mce.2015.08.018
    [21] K. A. Michaelis, A. J. Knox, M. Xu, K. Kiseljak-Vassiliades, M. G. Edwards, M. Geraci, et al., Identification of growth arrest and DNA-damage-inducible gene beta (GADD45beta) as a novel tumor suppressor in pituitary gonadotrope tumors, Endocrinology, 152 (2011), 3603-3613.
    [22] Z. R. Wu, L. Yan, Y. T. Liu, L. Cao, Y. H. Guo, Y. Zhang, et al., Inhibition of mTORC1 by lncRNA H19 via disrupting 4E-BP1/Raptor interaction in pituitary tumours, Nat. Commun., 9 (2018), 4624.
    [23] D. Fu, Y. Zhang, H. Cui, Long noncoding RNA CCAT2 is activated by E2F1 and exerts oncogenic properties by interacting with PTTG1 in pituitary adenomas, Am. J. Cancer Res., 8 (2018), 245-255.
    [24] W. Xing, Z. Qi, C. Huang, N. Zhang, W. Zhang, Y. Li, et al., Genome-wide identification of lncRNAs and mRNAs differentially expressed in non-functioning pituitary adenoma and construction of a lncRNA-mRNA co-expression network, Biol. Open, 8 (2019), bio037127.
    [25] L. Jin, Q. Cai, S. Wang, S. Wang, T. Mondal, J. Wang, et al., Long noncoding RNA MEG3 regulates LATS2 by promoting the ubiquitination of EZH2 and inhibits proliferation and invasion in gallbladder cancer, Cell Death Dis., 9 (2018), 1017.
    [26] Z. Li, C. Li, C. Liu, S. Yu, Y. Zhang, Expression of the long non-coding RNAs MEG3, HOTAIR, and MALAT-1 in non-functioning pituitary adenomas and their relationship to tumor behavior, Pituitary, 18 (2015), 42-47.
    [27] K. She, J. Huang, H. Zhou, T. Huang, G. Chen, J. He, LncRNA-SNHG7 promotes the proliferation, migration and invasion and inhibits apoptosis of lung cancer cells by enhancing the FAIM2 expression, Oncol. Rep., 36 (2016), 2673-2680.
    [28] M. W. Wang, J. Liu, Q. Liu, Q. H. Xu, T. F. Li, S. Jin, et al., LncRNA SNHG7 promotes the proliferation and inhibits apoptosis of gastric cancer cells by repressing the P15 and P16 expression, Eur. Rev. Med. Pharmacol. Sci., 21 (2017), 4613-4622
    [29] X. Zhong, Z. Long, S. Wu, M. Xiao, W. Hu, LncRNA-SNHG7 regulates proliferation, apoptosis and invasion of bladder cancer cells assurance guidelines, J. BU ON, 23 (2018), 776-781
    [30] A. M. Schmitt, H. Y. Chang, Long Noncoding RNAs in Cancer Pathways, Cancer Cell, 29 (2016), 452-463.
    [31] C. Chu, Q. C. Zhang, S. T. da Rocha, R. A. Flynn, M. Bharadwaj, J. M. Calabrese, et al., Systematic discovery of Xist RNA binding proteins, Cell, 161 (2015), 404-416.
    [32] X. F. Zhang, Y. Ye, S. J. Zhao, LncRNA Gas5 acts as a ceRNA to regulate PTEN expression by sponging miR-222-3p in papillary thyroid carcinoma, Oncotarget, 9 (2018), 3519-3530.
    [33] K. Zhang, J. Chen, H. Song, L. B. Chen, SNHG16/miR-140-5p axis promotes esophagus cancer cell proliferation, migration and EMT formation through regulating ZEB1, Oncotarget, 9 (2017), 1028-1040.
    [34] Z. Dong, P. Yang, X. Qiu, S. Liang, B. Guan, H. Yang, et al., KCNQ1OT1 facilitates progression of non-small-cell lung carcinoma via modulating miRNA-27b-3p/HSP90AA1 axis, J. Cell. Physiol., 234 (2019), 11304-11314.
    [35] W. Feng, C. Wang, C. Liang, H. Yang, D. Chen, X. Yu, et al., The Dysregulated Expression of KCNQ1OT1 and Its Interaction with Downstream Factors miR-145/CCNE2 in Breast Cancer Cells, Cell. Physiol. Biochem., 49 (2018), 432-446.
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