lncRNA TTN‑AS1 upregulates RUNX1 to enhance glioma progression via sponging miR‑27b‑3p

Chang,Keliang; Wang,Genwei; Lou,Jinfeng; Hao,Sha; Lv,Ranbo; Duan,Desheng; Zhang,Wanhong; Guo,Yingchang; Wang,Pengfei

doi:10.3892/or.2020.7684

lncRNA TTN‑AS1 upregulates RUNX1 to enhance glioma progression via sponging miR‑27b‑3p

Authors:
- Keliang Chang
- Genwei Wang
- Jinfeng Lou
- Sha Hao
- Ranbo Lv
- Desheng Duan
- Wanhong Zhang
- Yingchang Guo
- Pengfei Wang
View Affiliations

Affiliations: Department of Neurosurgery, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China, Department of Oncology, The Traditional Chinese Medicine Hospital of Jingmen, Jingmen, Hubei 448000, P.R. China, Department of Neurosurgery, Longhai Hospital of Kaifeng City, Kaifeng, Henan 475000, P.R. China, Department of Orthopaedics, The Third People's Hospital of Anyang, Anyang, Henan 455000, P.R. China, Department of Neurosurgery, Kaifeng Central Hospital, Kaifeng, Henan 475000, P.R. China, Department of Intervention Therapy, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China, Department of Neurosurgery, The People's Hospital of Pingyu, Pingyu, Henan 463400, P.R. China
Published online on: July 10, 2020 https://doi.org/10.3892/or.2020.7684
Pages: 1064-1074
Copyright: © Chang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Long non‑coding RNAs (lncRNAs) contribute to the tumorigeneses of numerous types of cancer, including glioma. The present study was designed to unveil a novel lncRNA functioning in glioma and explore the underlying mechanisms. lncRNA titin‑antisense RNA1 (TTN‑AS1), miR‑27b‑3p and Runt‑related transcription factor 1 (RUNX1) expression in glioma tissues and cell lines was estimated by RT‑qPCR. Si‑TTN‑AS1 was transfected into glioma cell lines (U251 and LN229), and CCK‑8 assay, flow cytometry, wound healing and Transwell assays were applied to estimate the function of TTN‑AS1 in glioma cells. miR‑27b‑3p inhibitor was used to explore the mechanisms. The results revealed that TTN‑AS1 was highly expressed in glioma specimens and cell lines. Downregulation of TTN‑AS1 inhibited the proliferation, migration and invasion of the glioma cells, as well as increased the rate of apoptosis. In vivo, the tumor growth was also inhibited by TTN‑AS1 depletion in nude mice. Furthermore, we revealed that TTN‑AS1 exerted oncogenic effects via sponging miR‑27b‑3p and thereby positively regulating RUNX1 expression. In conclusion, the present study supported that TTN‑AS1 acts as an oncogene in glioma by targeting miR‑27b‑3p to release RUNX1. This finding may contribute to gene therapy of glioma.

View Figures

View References

1	Strepkos D, Markouli M, Klonou A, Piperi C and Papavassiliou AG: Insights in the immunobiology of glioblastoma. J Mol Med (Berl). 98:1–10. 2019. View Article : Google Scholar : PubMed/NCBI
2	Ahammed Muneer KV, Rajendran VR and K PJ: Glioma tumor grade identification using artificial intelligent techniques. J Med Syst. 43:1132019. View Article : Google Scholar : PubMed/NCBI
3	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2018. CA Cancer J Clin. 68:7–30. 2018. View Article : Google Scholar : PubMed/NCBI
4	Ponting CP, Oliver PL and Reik W: Evolution and functions of long noncoding RNAs. Cell. 136:629–641. 2009. View Article : Google Scholar : PubMed/NCBI
5	Bhan A, Soleimani M and Mandal SS: Long noncoding RNA and xancer: A new paradigm. Cancer Res. 77:3965–3981. 2017. View Article : Google Scholar : PubMed/NCBI
6	Zhu Y, Tong Y, Wu J, Liu Y and Zhao M: Knockdown of LncRNA GHET1 suppresses prostate cancer cell proliferation by inhibiting HIF-1α/Notch-1 signaling pathway via KLF2. Biofactors. 45:364–373. 2019. View Article : Google Scholar : PubMed/NCBI
7	Wang Y, Jiang F, Xiong Y, Cheng X, Qiu Z and Song R: LncRNA TTN-AS1 sponges miR-376a-3p to promote colorectal cancer progression via upregulating KLF15. Life Sci. 244:1169362020. View Article : Google Scholar : PubMed/NCBI
8	Fei F, He Y, He S, He Z, Wang Y, Wu G and Li M: LncRNA SNHG3 enhances the malignant progress of glioma through silencing KLF2 and p21. Biosci Rep. 38:BSR201804202018. View Article : Google Scholar : PubMed/NCBI
9	Liao Y, Shen L, Zhao H, Liu Q, Fu J, Guo Y, Peng R and Cheng L: LncRNA CASC2 interacts with miR-181a to modulate glioma growth and resistance to TMZ through PTEN pathway. J Cell Biochem. 118:1889–1899. 2017. View Article : Google Scholar : PubMed/NCBI
10	Tang F, Wang H, Chen E, Bian E, Xu Y, Ji X, Yang Z, Hua X, Zhang Y and Zhao B: LncRNA-ATB promotes TGF-β-induced glioma cells invasion through NF-κB and P38/MAPK pathway. J Cell Physiol. 234:23302–23314. 2019. View Article : Google Scholar : PubMed/NCBI
11	Ding M, Liu Y, Liao X, Zhan H, Liu Y and Huang W: Enhancer RNAs (eRNAs): New insights into gene transcription and disease treatment. J Cancer. 9:2334–2340. 2018. View Article : Google Scholar : PubMed/NCBI
12	Zaheer U, Faheem M, Qadri I, Begum N, Yassine HM, Al Thani AA and Mathew S: Expression profile of MicroRNA: An emerging hallmark of cancer. Curr Pharm Des. 25:642–653. 2019. View Article : Google Scholar : PubMed/NCBI
13	Hu G, Liu N, Wang H, Wang Y and Guo Z: LncRNA LINC01857 promotes growth, migration, and invasion of glioma by modulating miR-1281/TRIM65 axis. J Cell Physiol. 234:22009–22016. 2019. View Article : Google Scholar : PubMed/NCBI
14	Zhao H, Peng R, Liu Q, Liu D, Du P, Yuan J, Peng G and Liao Y: The lncRNA H19 interacts with miR-140 to modulate glioma growth by targeting iASPP. Arch Biochem Biophys. 610:1–7. 2016. View Article : Google Scholar : PubMed/NCBI
15	Zhang Q, Wang G, Xu L, Yao Z and Song L: Long non-coding RNA LINC00473 promotes glioma cells proliferation and invasion by impairing miR-637/CDK6 axis. Artif Cells Nanomed Biotechnol. 47:3896–3903. 2019. View Article : Google Scholar : PubMed/NCBI
16	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
17	Li JH, Liu S, Zhou H, Qu LH and Yang JH: starBase v2.0: Decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res. 42(D1): D92–D97. 2014. View Article : Google Scholar : PubMed/NCBI
18	Dang Y, Wei X, Xue L, Wen F, Gu J and Zheng H: Long non-coding RNA in glioma: Target miRNA and signaling pathways. Clin Lab. 64:887–894. 2018. View Article : Google Scholar : PubMed/NCBI
19	Lin C, Zhang S, Wang Y, Wang Y, Nice E, Guo C, Zhang E, Yu L, Li M, Liu C, et al: Functional role of a novel long noncoding RNA TTN-AS1 in esophageal squamous cell carcinoma progression and metastasis. Clin Cancer Res. 24:486–498. 2018. View Article : Google Scholar : PubMed/NCBI
20	Cui Z, Luo Z, Lin Z, Shi L, Hong Y and Yan C: Long non-coding RNA TTN-AS1 facilitates tumorigenesis of papillary thyroid cancer through modulating the miR-153-3p/ZNRF2 axis. J Gene Med. 21:e30832019. View Article : Google Scholar : PubMed/NCBI
21	Li S, Liu F, Pei Y, Wang W, Zheng K and Zhang X: Long noncoding RNA TTN-AS1 enhances the malignant characteristics of osteosarcoma by acting as a competing endogenous RNA on microRNA-376a thereby upregulating dickkopf-1. Aging (Albany NY). 11:7678–7693. 2019.PubMed/NCBI
22	Xu Y, Han YF, Ye B, Zhang YL, Dong JD, Zhu SJ and Chen J: miR-27b-3p is involved in doxorubicin resistance of human anaplastic thyroid cancer cells via targeting peroxisome proliferator-activated receptor gamma. Basic Clin Pharmacol Toxicol. 123:670–677. 2018. View Article : Google Scholar : PubMed/NCBI
23	Liu L, Hu J, Yu T, You S, Zhang Y and Hu L: miR-27b-3p/MARCH7 regulates invasion and metastasis of endometrial cancer cells through Snail-mediated pathway. Acta Biochim Biophys Sin (Shanghai). 51:492–500. 2019. View Article : Google Scholar : PubMed/NCBI
24	Zhang R, Li JB, Yan XF, Jin K, Li WY, Xu J, Zhao J, Bai JH and Chen YZ: Increased EWSAT1 expression promotes cell proliferation, invasion and epithelial-mesenchymal transition in colorectal cancer. Eur Rev Med Pharmacol Sci. 22:6801–6808. 2018.PubMed/NCBI
25	Wang M, Qiu Y, Zhang R, Gao L, Wang X, Bi L and Wang Y: MEHP promotes the proliferation of oral cancer cells via down regulation of miR-27b-5p and miR-372-5p. Toxicol In Vitro. 58:35–41. 2019. View Article : Google Scholar : PubMed/NCBI
26	Liang H, Ai-Jun J, Ji-Zong Z, Jian-Bo H, Liang Z, Yong-Xiang Y and Chen Y: Clinicopathological significance of miR-27b targeting Golgi protein 73 in patients with hepatocellular carcinoma. Anticancer Drugs. 30:186–194. 2019. View Article : Google Scholar : PubMed/NCBI
27	Chen Y, Zhang B, Jin Y, Wu Q and Cao L: MiR-27b targets PI3K p110α to inhibit proliferation and migration in colorectal cancer stem cell. Am J Transl Res. 11:5988–5997. 2019.PubMed/NCBI
28	Hong D, Fritz AJ, Gordon JA, Tye CE, Boyd JR, Tracy KM, Frietze SE, Carr FE, Nickerson JA, Van Wijnen AJ, et al: RUNX1-dependent mechanisms in biological control and dysregulation in cancer. J Cell Physiol. 234:8597–8609. 2019. View Article : Google Scholar : PubMed/NCBI
29	Chen K and Pan G: Dysregulation of microRNA-106a-5p-RUNX1 axis associates with clinical progression and prognosis of osteosarcoma patients. Pathol Res Pract. 215:1526862019. View Article : Google Scholar : PubMed/NCBI
30	Fu Y, Sun S, Man X and Kong C: Increased expression of RUNX1 in clear cell renal cell carcinoma predicts poor prognosis. PeerJ. 7:e78542019. View Article : Google Scholar : PubMed/NCBI
31	Keita M, Bachvarova M, Morin C, Plante M, Gregoire J, Renaud MC, Sebastianelli A, Trinh XB and Bachvarov D: The RUNX1 transcription factor is expressed in serous epithelial ovarian carcinoma and contributes to cell proliferation, migration and invasion. Cell Cycle. 12:972–986. 2013. View Article : Google Scholar : PubMed/NCBI
32	Zhou T, Luo M, Cai W, Zhou S, Feng D, Xu C and Wang H: Runt-related transcription factor 1 (RUNX1) promotes TGF-β-induced renal ttubular epithelial-to-mesenchymal transition (EMT) and renal fibrosis through the PI3K subunit p110δ. EBioMedicine. 31:217–225. 2018. View Article : Google Scholar : PubMed/NCBI
33	Alonso-Alconada L, Muinelo-Romay L, Madissoo K, Diaz-Lopez A, Krakstad C, Trovik J, Wik E, Hapangama D, Coenegrachts L, Cano A, et al: ENITEC Consortium: Molecular profiling of circulating tumor cells links plasticity to the metastatic process in endometrial cancer. Mol Cancer. 13:2232014. View Article : Google Scholar : PubMed/NCBI
34	Scheitz CJF, Lee TS, McDermitt DJ and Tumbar T: Defining a tissue stem cell-driven Runx1/Stat3 signalling axis in epithelial cancer. EMBO J. 31:4124–4139. 2012. View Article : Google Scholar : PubMed/NCBI