Abstract
Purpose
The current study aimed to investigate the role of long intergenic noncoding 01433 (LINC01433) in the proliferation, migration and invasion of nasopharyngeal carcinoma (NPC).
Methods
Real-time quantitative PCR (RT-qPCR) was performed to determine the expressions of LINC01433 and miR-506-3p in NPC samples and cell lines. The effects of LINC01433 on cell proliferation, migration and invasion were measured by CCK-8, wound healing assay and Transwell, respectively. In addition, Pearson correlation analysis, starBase, RNA immunoprecipitation, luciferase assay, Western blot and functional experiments were conducted to detect and confirm the relationship between LINC01433 and miR-506-3p.
Results
LINC01433 level was noticeably elevated in NPC tissues and cell lines. As the expression of LINC01433 in 5-8F cells was the highest in NPC cell lines and the expression of LINC01433 in SUNE1 cells was the lowest, 5-8F and SUNE1 cells were therefore selected as the target cells for following experiments. Furthermore, miR-506-3p was predicted as the target of LINC01433, and the two were negatively correlated with each other. Interestingly, overexpression of LINC01433 promoted proliferation, migration and invasion of NPC cells, while miR-506-3p reversed such effects of LINC01433. Moreover, LINC01433 silencing had the opposite effects to LINC01433 overexpression. Furthermore, miR-506-3p overexpression inhibited the expressions of MMP2, N-cadherin, p-PI3K and p-Akt, and promoted the expressions of E-cadherin and TIMP-2, and partially reversed the role of LINC01433 in promoting cancer development.
Conclusion
The current findings reveal that LINC01433 regulates NPC cell biological progress through miR-506-3p.
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Availability of data and materials
The analyzed data sets generated during the study are available from the corresponding author on reasonable request.
References
- 1.
Paul P, Deka H, Malakar AK, Halder B, Chakraborty S (2018) Nasopharyngeal carcinoma: understanding its molecular biology at a fine scale. Eur J Cancer Prevent 27(1):33–41. https://doi.org/10.1097/cej.0000000000000314
- 2.
Chua MLK, Wee JTS, Hui EP, Chan ATC (2016) Nasopharyngeal carcinoma. Lancet (Lond, Engl) 387(10022):1012–1024. https://doi.org/10.1016/s0140-6736(15)00055-0
- 3.
Renganathan A, Felley-Bosco E (2017) Long noncoding RNAs in cancer and therapeutic potential. Adv Exp Med Biol 1008:199–222. https://doi.org/10.1007/978-981-10-5203-3_7
- 4.
Cai Z, Xu K, Li Y, Lv Y, Bao J, Qiao L (2017) Long noncoding RNA in liver cancer stem cells. Discov Med 24(131):87–93
- 5.
Li J, Li Z, Zheng W, Li X, Wang Z, Cui Y, Jiang X (2017) LncRNA-ATB: An indispensable cancer-related long noncoding RNA. Cell Prolif 50:6. https://doi.org/10.1111/cpr.12381
- 6.
Wang J, Su Z, Lu S, Fu W, Liu Z, Jiang X, Tai S (2018) LncRNA HOXA-AS2 and its molecular mechanisms in human cancer. Clin Chim Acta 485:229–233. https://doi.org/10.1016/j.cca.2018.07.004
- 7.
Huang HW, Xie H, Ma X, Zhao F, Gao Y (2017) Upregulation of LncRNA PANDAR predicts poor prognosis and promotes cell proliferation in cervical cancer. Eur Rev Med Pharmacol Sci 21(20):4529–4535
- 8.
Geng YJ, Xie SL, Li Q, Ma J, Wang GY (2011) Large intervening non-coding RNA HOTAIR is associated with hepatocellular carcinoma progression. J Int Med Res 39(6):2119–2128. https://doi.org/10.1177/147323001103900608
- 9.
Zhang R, Xia Y, Wang Z, Zheng J, Chen Y, Li X, Wang Y, Ming H (2017) Serum long non coding RNA MALAT-1 protected by exosomes is up-regulated and promotes cell proliferation and migration in non-small cell lung cancer. Biochem Biophys Res Commun 490(2):406–414. https://doi.org/10.1016/j.bbrc.2017.06.055
- 10.
He R, Hu Z, Wang Q, Luo W, Li J, Duan L, Zhu YS, Luo DX (2017) The role of long non-coding RNAs in nasopharyngeal carcinoma: as systemic review. Oncotarget 8(9):16075–16083. https://doi.org/10.18632/oncotarget.14211
- 11.
Sun Q, Liu H, Li L, Zhang S, Liu K, Liu Y, Yang C (2015) Long noncoding RNA-LET, which is repressed by EZH2, inhibits cell proliferation and induces apoptosis of nasopharyngeal carcinoma cell. Med Oncol (Northwood, Lond, Engl) 32(9):226. https://doi.org/10.1007/s12032-015-0673-0
- 12.
Yang QQ, Deng YF (2015) Genome-wide analysis of long non-coding RNA in primary nasopharyngeal carcinoma by microarray. Histopathology 66(7):1022–1030. https://doi.org/10.1111/his.12616
- 13.
Nie Y, Liu X, Qu S, Song E, Zou H, Gong C (2013) Long non-coding RNA HOTAIR is an independent prognostic marker for nasopharyngeal carcinoma progression and survival. Cancer Sci 104(4):458–464. https://doi.org/10.1111/cas.12092
- 14.
Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P, Ballew RM, Huson DH, Wortman JR, Zhang Q, Kodira CD, Zheng XH, Chen L, Skupski M, Subramanian G, Thomas PD, Zhang J, Gabor Miklos GL, Nelson C, Broder S, Clark AG, Nadeau J, McKusick VA, Zinder N, Levine AJ, Roberts RJ, Simon M, Slayman C, Hunkapiller M, Bolanos R, Delcher A, Dew I, Fasulo D, Flanigan M, Florea L, Halpern A, Hannenhalli S, Kravitz S, Levy S, Mobarry C, Reinert K, Remington K, Abu-Threideh J, Beasley E, Biddick K, Bonazzi V, Brandon R, Cargill M, Chandramouliswaran I, Charlab R, Chaturvedi K, Deng Z, Di Francesco V, Dunn P, Eilbeck K, Evangelista C, Gabrielian AE, Gan W, Ge W, Gong F, Gu Z, Guan P, Heiman TJ, Higgins ME, Ji RR, Ke Z, Ketchum KA, Lai Z, Lei Y, Li Z, Li J, Liang Y, Lin X, Lu F, Merkulov GV, Milshina N, Moore HM, Naik AK, Narayan VA, Neelam B, Nusskern D, Rusch DB, Salzberg S, Shao W, Shue B, Sun J, Wang Z, Wang A, Wang X, Wang J, Wei M, Wides R, Xiao C, Yan C, Yao A, Ye J, Zhan M, Zhang W, Zhang H, Zhao Q, Zheng L, Zhong F, Zhong W, Zhu S, Zhao S, Gilbert D, Baumhueter S, Spier G, Carter C, Cravchik A, Woodage T, Ali F, An H, Awe A, Baldwin D, Baden H, Barnstead M, Barrow I, Beeson K, Busam D, Carver A, Center A, Cheng ML, Curry L, Danaher S, Davenport L, Desilets R, Dietz S, Dodson K, Doup L, Ferriera S, Garg N, Gluecksmann A, Hart B, Haynes J, Haynes C, Heiner C, Hladun S, Hostin D, Houck J, Howland T, Ibegwam C, Johnson J, Kalush F, Kline L, Koduru S, Love A, Mann F, May D, McCawley S, McIntosh T, McMullen I, Moy M, Moy L, Murphy B, Nelson K, Pfannkoch C, Pratts E, Puri V, Qureshi H, Reardon M, Rodriguez R, Rogers YH, Romblad D, Ruhfel B, Scott R, Sitter C, Smallwood M, Stewart E, Strong R, Suh E, Thomas R, Tint NN, Tse S, Vech C, Wang G, Wetter J, Williams S, Williams M, Windsor S, Winn-Deen E, Wolfe K, Zaveri J, Zaveri K, Abril JF, Guigo R, Campbell MJ, Sjolander KV, Karlak B, Kejariwal A, Mi H, Lazareva B, Hatton T, Narechania A, Diemer K, Muruganujan A, Guo N, Sato S, Bafna V, Istrail S, Lippert R, Schwartz R, Walenz B, Yooseph S, Allen D, Basu A, Baxendale J, Blick L, Caminha M, Carnes-Stine J, Caulk P, Chiang YH, Coyne M, Dahlke C, Mays A, Dombroski M, Donnelly M, Ely D, Esparham S, Fosler C, Gire H, Glanowski S, Glasser K, Glodek A, Gorokhov M, Graham K, Gropman B, Harris M, Heil J, Henderson S, Hoover J, Jennings D, Jordan C, Jordan J, Kasha J, Kagan L, Kraft C, Levitsky A, Lewis M, Liu X, Lopez J, Ma D, Majoros W, McDaniel J, Murphy S, Newman M, Nguyen T, Nguyen N, Nodell M, Pan S, Peck J, Peterson M, Rowe W, Sanders R, Scott J, Simpson M, Smith T, Sprague A, Stockwell T, Turner R, Venter E, Wang M, Wen M, Wu D, Wu M, Xia A, Zandieh A, Zhu X (2001) The sequence of the human genome. Science 291(5507):1304–1351. https://doi.org/10.1126/science.1058040
- 15.
Qian B, Wang X, Mao C, Jiang Y, Shi Y, Chen L, Liu S, Wang B, Pan S, Tao Y, Shi H (2018) Long non-coding RNA linc01433 promotes migration and invasion in non-small cell lung cancer. Thorac Cancer 9(5):589–597. https://doi.org/10.1111/1759-7714.12623
- 16.
Wu M, Wu W, Ding J, Yang J (2019) LINC01433/miR-2116-3p/MYC feedback loop promotes cell proliferation, migration, and the epithelial-mesenchymal transition in breast cancer. Cancer Biotherapy Radiopharmaceut 34(6):388–397. https://doi.org/10.1089/cbr.2019.2772
- 17.
Zhang A, Xu M, Mo YY (2014) Role of the lncRNA-p53 regulatory network in cancer. J Mol Cell Biol 6(3):181–191. https://doi.org/10.1093/jmcb/mju013
- 18.
Ballantyne MD, McDonald RA, Baker AH (2016) lncRNA/MicroRNA interactions in the vasculature. Clin Pharmacol Ther 99(5):494–501. https://doi.org/10.1002/cpt.355
- 19.
Kong YG, Cui M, Chen SM, Xu Y, Xu Y, Tao ZZ (2018) LncRNA-LINC00460 facilitates nasopharyngeal carcinoma tumorigenesis through sponging miR-149-5p to up-regulate IL6. Gene 639:77–84. https://doi.org/10.1016/j.gene.2017.10.006
- 20.
Huang H, Bu YZ, Zhang XY, Liu J, Zhu LY, Fang Y (2019) LINC01433 promotes hepatocellular carcinoma progression via modulating the miR-1301/STAT3 axis. J Cell Physiol 234(5):6116–6124. https://doi.org/10.1002/jcp.27366
- 21.
Rio DC, Ares M Jr, Hannon GJ (2010) Nilsen TW (2010) Purification of RNA using TRIzol (TRI reagent). Cold Spring Harbor Protocols 6:5439. https://doi.org/10.1101/pdb.prot5439
- 22.
Xie L, Hu Z, Wang X, Li Z (2013) Expression of long noncoding RNA MALAT1 gene in human nasopharyngeal carcinoma cell lines and its biological significance. J Southern Med Univ 33(5):692–697
- 23.
Bo H, Gong Z, Zhang W, Li X, Zeng Y, Liao Q, Chen P, Shi L, Lian Y, Jing Y, Tang K, Li Z, Zhou Y, Zhou M, Xiang B, Li X, Yang J, Xiong W, Li G, Zeng Z (2015) Upregulated long non-coding RNA AFAP1-AS1 expression is associated with progression and poor prognosis of nasopharyngeal carcinoma. Oncotarget 6(24):20404–20418. https://doi.org/10.18632/oncotarget.4057
- 24.
Liang WC, Fu WM, Wong CW, Wang Y, Wang WM, Hu GX, Zhang L, Xiao LJ, Wan DC, Zhang JF, Waye MM (2015) The lncRNA H19 promotes epithelial to mesenchymal transition by functioning as miRNA sponges in colorectal cancer. Oncotarget 6(26):22513–22525. https://doi.org/10.18632/oncotarget.4154
- 25.
Zhang W, Wang L, Zheng F, Zou R, Xie C, Guo Q, Hu Q, Chen J, Yang X, Yao H, Song E, Xiang Y (2015) Long noncoding RNA expression signatures of metastatic nasopharyngeal carcinoma and their prognostic value. Biomed Res Int 2015:618924. https://doi.org/10.1155/2015/618924
- 26.
Zhang S, Zhong G, He W, Yu H, Huang J, Lin T (2016) lncRNA up-regulated in nonmuscle invasive bladder cancer facilitates tumor growth and acts as a negative prognostic factor of recurrence. J Urol 196(4):1270–1278. https://doi.org/10.1016/j.juro.2016.05.107
- 27.
Nie GH, Li Z, Duan HF, Luo L, Hu HY, Yang WQ, Nie LP, Zhu RF, Chen XF, Zhang W (2017) lncRNA C22orf32-1 contributes to the tumorigenesis of nasopharyngeal carcinoma. Oncol Lett 13(6):4487–4492. https://doi.org/10.3892/ol.2017.6021
- 28.
Ma DD, Yuan LL, Lin LQ (2017) LncRNA HOTAIR contributes to the tumorigenesis of nasopharyngeal carcinoma via up-regulating FASN. Eur Rev Med Pharmacol Sci 21(22):5143–5152. https://doi.org/10.26355/eurrev_201711_13831
- 29.
Zhang C, Qian H, Liu K, Zhao W, Wang L (2019) A Feedback loop regulation of LINC01433 and YAP promotes malignant behavior in gastric cancer cells. OncoTargets Therapy 12:7949–7962. https://doi.org/10.2147/OTT.S222903
- 30.
Qadir MI, Faheem A (2017) miRNA: a diagnostic and therapeutic tool for pancreatic cancer. Crit Rev Eukaryot Gene Expr 27(3):197–204. https://doi.org/10.1615/CritRevEukaryotGeneExpr.2017019494
- 31.
Puik JR, Meijer LL, Le Large TY, Prado MM, Frampton AE, Kazemier G, Giovannetti E (2017) miRNA profiling for diagnosis, prognosis and stratification of cancer treatment in cholangiocarcinoma. Pharmacogenomics 18(14):1343–1358. https://doi.org/10.2217/pgs-2017-0010
- 32.
Yu F, Lv M, Li D, Cai H, Ma L, Luo Q, Yuan X, Lv Z (2015) MiR-506 over-expression inhibits proliferation and metastasis of breast cancer cells. Med Sci Monitor 21:1687–1692. https://doi.org/10.12659/msm.893522
- 33.
Yao J, Qin L, Miao S, Wang X, Wu X (2016) Overexpression of miR-506 suppresses proliferation and promotes apoptosis of osteosarcoma cells by targeting astrocyte elevated gene-1. Oncol Lett 12(3):1840–1848. https://doi.org/10.3892/ol.2016.4827
- 34.
Luo Y, Sun R, Zhang J, Sun T, Liu X, Yang B (2015) miR-506 inhibits the proliferation and invasion by targeting IGF2BP1 in glioblastoma. Am J Transl Res 7(10):2007–2014
- 35.
Erice O, Munoz-Garrido P, Vaquero J, Perugorria MJ, Fernandez-Barrena MG, Saez E, Santos-Laso A, Arbelaiz A, Jimenez-Aguero R, Fernandez-Irigoyen J, Santamaria E, Torrano V, Carracedo A, Ananthanarayanan M, Marzioni M, Prieto J, Beuers U, Oude Elferink RP, LaRusso NF, Bujanda L, Marin JJG, Banales JM (2018) MicroRNA-506 promotes primary biliary cholangitis-like features in cholangiocytes and immune activation. Hepatol (Baltim) 67(4):1420–1440. https://doi.org/10.1002/hep.29533
- 36.
Gong M, Chen C, Zhao H, Sun M, Song M (2018) miR-506 suppresses cervical cancer cell proliferation both in vitro and in vivo. Neoplasma 65(3):331–338. https://doi.org/10.4149/neo_2018_170112N25
- 37.
Liu G, Sun Y, Ji P, Li X, Cogdell D, Yang D, Parker Kerrigan BC, Shmulevich I, Chen K, Sood AK, Xue F, Zhang W (2014) MiR-506 suppresses proliferation and induces senescence by directly targeting the CDK4/6-FOXM1 axis in ovarian cancer. J Pathol 233(3):308–318. https://doi.org/10.1002/path.4348
- 38.
Zhang Z, Ma J, Luan G, Kang L, Su Y, He Y, Luan F (2015) MiR-506 suppresses tumor proliferation and invasion by targeting FOXQ1 in nasopharyngeal carcinoma. PLoS ONE 10(4):e0122851. https://doi.org/10.1371/journal.pone.0122851
- 39.
Li J, Ju J, Ni B, Wang H (2016) The emerging role of miR-506 in cancer. Oncotarget 7(38):62778–62788. https://doi.org/10.18632/oncotarget.11294
- 40.
Liang TS, Zheng YJ, Wang J, Zhao JY, Yang DK, Liu ZS (2019) MicroRNA-506 inhibits tumor growth and metastasis in nasopharyngeal carcinoma through the inactivation of the Wnt/beta-catenin signaling pathway by down-regulating LHX2. J Exp Clin Cancer Res 38(1):97. https://doi.org/10.1186/s13046-019-1023-4
- 41.
Feng X, Zhang C, Zhu L, Zhang L, Li H, He L, Mi Y, Wang Y, Zhu J, Bu Y (2017) DEPDC1 is required for cell cycle progression and motility in nasopharyngeal carcinoma. Oncotarget 8(38):63605–63619. https://doi.org/10.18632/oncotarget.18868
- 42.
Lawicki S, Zajkowska M, Glazewska EK, Bedkowska GE, Szmitkowski M (2017) Plasma levels and diagnostic utility of VEGF, MMP-2 and TIMP-2 in the diagnostics of breast cancer patients. Biomarkers 22(2):157–164. https://doi.org/10.1080/1354750x.2016.1252955
- 43.
Shrestha B, Bajracharya D, Byatnal AA, Kamath A, Radhakrishnan R (2017) May High MMP-2 and TIMP-2 expressions increase or decrease the aggressivity of oral cancer? Pathol Oncol Res 23(1):197–206. https://doi.org/10.1007/s12253-016-0149-3
- 44.
Yi GZ, Feng WY, Zhou Q, Liu YW, Qi ST (2017) The impact of MMP-2 and its specific inhibitor TIMP-2 expression on the WHO grade and prognosis of gliomas in Chinese population: a meta-analysis. Mol Neurobiol 54(1):22–30. https://doi.org/10.1007/s12035-015-9539-x
- 45.
Wang T, Hou J, Jian S, Luo Q, Wei J, Li Z, Wang X, Bai P, Duan B, Xing J, Cai J (2018) miR-29b negatively regulates MMP2 to impact gastric cancer development by suppress gastric cancer cell migration and tumor growth. J Cancer 9(20):3776–3786. https://doi.org/10.7150/jca.26263
- 46.
Lei H, Gao Y, Xu X (2017) LncRNA TUG1 influences papillary thyroid cancer cell proliferation, migration and EMT formation through targeting miR-145. Acta Biochim Biophys Sin 49(7):588–597. https://doi.org/10.1093/abbs/gmx047
- 47.
Derycke LD, Bracke ME (2004) N-cadherin in the spotlight of cell-cell adhesion, differentiation, embryogenesis, invasion and signalling. Int J Develop Biol 48(5–6):463–476. https://doi.org/10.1387/ijdb.041793ld
- 48.
Blaschuk OW (2015) N-cadherin antagonists as oncology therapeutics. Philos Trans R Soc Lond B Biol Sci 370(1661):20140039. https://doi.org/10.1098/rstb.2014.0039
- 49.
Petrova YI, Schecterson L, Gumbiner BM (2016) Roles for E-cadherin cell surface regulation in cancer. Mol Biol Cell 27(21):3233–3244. https://doi.org/10.1091/mbc.E16-01-0058
- 50.
Zhu Y, Yan L, Zhu W, Song X, Yang G, Wang S (2019) MMP2/3 promote the growth and migration of laryngeal squamous cell carcinoma via PI3K/Akt-NF-kappaB-mediated epithelial-mesenchymal transformation. J Cell Physiol. https://doi.org/10.1002/jcp.28242
- 51.
Kolude B, Adisa AO, Lawal AO, Adeyemi BF, Akinyamoju AO (2015) Stoichiometric expression of MMP-2/TIMP-2 in benign and malignant tumours of the salivary gland. Tumour Biol 36(4):2351–2357. https://doi.org/10.1007/s13277-014-2842-8
- 52.
Xia P, Xu XY (2015) PI3K/Akt/mTOR signaling pathway in cancer stem cells: from basic research to clinical application. Am J Cancer Res 5(5):1602–1609
Funding
This work was supported by the Scientific Research Project of Zhejiang Educational Committee [Grant no. Y201636243].
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Substantial contributions to conception and design: MZ. Data acquisition, data analysis and interpretation: ZD, SH, MX. Drafting the article or critically revising it for important intellectual content: MZ. Final approval of the version to be published: All authors. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of the work are appropriately investigated and resolved: All authors.
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Zhou, M., Dong, Z., Hu, S. et al. LINC01433 targets miR-506-3p to promote the biological progress of nasopharyngeal carcinoma cells. Eur Arch Otorhinolaryngol (2021). https://doi.org/10.1007/s00405-021-06607-w
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Keywords
- LINC01433
- miR-506-3p
- Nasopharyngeal carcinoma
- Proliferation
- Migration