Oncogenic miR-19a and miR-19b co-regulate tumor suppressor MTUS1 to promote cell proliferation and migration in lung cancer

doi:10.1007/s13238-017-0393-7

Protein Cell

2017, Vol. 8

Issue (6) : 455-466 https://doi.org/10.1007/s13238-017-0393-7

RESEARCH ARTICLE

Oncogenic miR-19a and miR-19b co-regulate tumor suppressor MTUS1 to promote cell proliferation and migration in lung cancer

Yuanyuan Gu¹, Shuoxin Liu², Xiaodan Zhang¹, Guimin Chen², Hongwei Liang¹, Mengchao Yu¹, Zhicong Liao³, Yong Zhou³, Chen-Yu Zhang¹, Tao Wang¹(

), Chen Wang¹(

), Junfeng Zhang¹(

), Xi Chen¹(

)

¹. State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for Micro, RNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing 210046, China
². The Second Department of Medical Oncology, Linyi Tumor Hospital, Linyi 276000, China
³. Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University and Nanjing Multi-Center Biobank, Nanjing 210008, China

Download: PDF(1586 KB)
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks

Abstract

MTUS1 (microtubule-associated tumor suppressor 1) has been identified that can function as a tumor suppressor gene in many malignant tumors. However, the function and mechanisms underlying the regulation of MTUS1 are unclear. In the present study, we reported that miR-19a and miR-19b (miR-19a/b) promote proliferation and migration of lung cancer cells by targeting MTUS1. First, MTUS1 was proved to function as a tumor suppressor in lung cancer and was linked to cell proliferation and migration promotion. Second, an inverse correlation between miR-19a/b expression and MTUS1 mRNA/protein expression was noted in human lung cancer tissues. Third, MTUS1 was appraised as a direct target of miR-19a/b by bioinformatics analysis. Fourth, direct MTUS1 regulation by miR-19a/b in lung cancer cells was experimentally affirmed by cell transfection assay and luciferase reporter assay. Finally, miR-19a/b were shown to cooperatively repress MTUS1 expression and synergistically regulate MTUS1 expression to promote lung cancer cell proliferation and migration. In conclusion, our findings have provided the first clues regarding the roles of miR-19a/b, which appear to function as oncomirs in lung cancer by downregulating MTUS1.

Keywords microRNA MTUS1 miR-19a/b lung cancer proliferation migration

Corresponding Author(s): Tao Wang,Chen Wang,Junfeng Zhang,Xi Chen

Issue Date: 05 July 2017

Cite this article:

Yuanyuan Gu,Shuoxin Liu,Xiaodan Zhang, et al. Oncogenic miR-19a and miR-19b co-regulate tumor suppressor MTUS1 to promote cell proliferation and migration in lung cancer[J]. Protein Cell, 2017, 8(6): 455-466.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-017-0393-7
https://academic.hep.com.cn/pac/EN/Y2017/V8/I6/455

1	AdamsBD, KasinskiAL, SlackFJ (2014) Aberrant regulation and function of microRNAs in cancer. Curr Biol24:R762–R776 https://doi.org/10.1016/j.cub.2014.06.043
2	AmbrosV (2004) The functions of animal microRNAs. Nature431:350–355 https://doi.org/10.1038/nature02871
3	BartelDP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell116:281–297 https://doi.org/10.1016/S0092-8674(04)00045-5
4	CalinGA, CroceCM (2006) MicroRNA signatures in human cancers. Nat Rev Cancer6:857–866 https://doi.org/10.1038/nrc1997
5	Di BenedettoM, BiecheI, DeshayesF, VacherS, NouetS, ColluraV, SeitzI, LouisS, PineauP, Amsellem-OuazanaDet al. (2006) Structural organization and expression of human MTUS1, a candidate 8p22 tumor suppressor gene encoding a family of angiotensin II AT2 receptor-interacting proteins, ATIP. Gene380:127–136 https://doi.org/10.1016/j.gene.2006.05.021
6	DingX, ZhangN, CaiY, LiS, ZhengC, JinY, YuT, WangA, ZhouX (2012) Down-regulation of tumor suppressor MTUS1/ATIP is associated with enhanced proliferation, poor differentiation and poor prognosis in oral tongue squamous cell carcinoma. Mol Oncol6:73–80 https://doi.org/10.1016/j.molonc.2011.11.002
7	GuinotA, Oeztuerk-WinderF, VenturaJJ (2016) miR-17-92/p38alpha dysregulation enhances Wnt signal and selects Lgr6+ cancer stem cell like cells during human lung adenocarcinoma progression. Cancer Res.
8	GuzM, Rivero-MullerA, OkonE, Stenzel-BembenekA, PolbergK, SlomkaM, StepulakA (2014) MicroRNAs-role in lung cancer. Dis Markers2014:218169 https://doi.org/10.1155/2014/218169
9	HeL, HannonGJ (2004) MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet5:522–531 https://doi.org/10.1038/nrg1379
10	KangSM, LeeHJ (2014) MicroRNAs in human lung cancer. Exp Biol Med (Maywood)239:1505–1513 https://doi.org/10.1177/1535370214533887
11	KinjoT, IsomuraM, IwamasaT, NakamuraY (2000)Molecular cloning and characterization of two novel genes on chromosome 8p21.3. J Hum Genet45:12–17 https://doi.org/10.1007/s100380050003
12	KnowleD, AhmedS, PulakatL (2000) Identification of an interaction between the angiotensin II receptor sub-type AT2 and the ErbB3 receptor, a member of the epidermal growth factor receptor family. Regul Pept87:73–82 https://doi.org/10.1016/S0167-0115(99)00111-1
13	LiX, LiuH, YuT, DongZ, TangL, SunX (2014a) Loss of MTUS1 in gastric cancer promotes tumor growth and metastasis. Neoplasma61:128–135 https://doi.org/10.4149/neo_2014_018
14	LiX, XieW, XieC, HuangC, ZhuJ, LiangZ, DengF, ZhuM, ZhuW, WuRet al. (2014b) Curcumin modulates miR-19/PTEN/AKT/p53 axis to suppress bisphenol A-induced MCF-7 breast cancer cell proliferation. Phytother Res28:1553–1560 https://doi.org/10.1002/ptr.5167
15	LouisSN, ChowL, RezmannL, KrezelMA, CattKJ, TikellisC, FraumanAG, LouisWJ (2010) Expression and function of ATIP/MTUS1 in human prostate cancer cell lines. Prostate70:1563–1574 https://doi.org/10.1002/pros.21192
16	LouisSN, ChowLT, VarghayeeN, RezmannLA, FraumanAG, LouisWJ (2011) The expression of MTUS1/ATIP and its major isoforms, ATIP1 and ATIP3, in human prostate cancer. Cancers (Basel)3:3824–3837 https://doi.org/10.3390/cancers3043824
17	LuWD, ZuoY, XuZ, ZhangM (2015) MiR-19a promotes epithelialmesenchymal transition through PI3K/AKT pathway in gastric cancer. World J Gastroenterol21:4564–4573
18	MaL, WeinbergRA (2008) Micromanagers of malignancy: role of microRNAs in regulating metastasis. Trends Genet24:448–456 https://doi.org/10.1016/j.tig.2008.06.004
19	MolinaA, Rodrigues-FerreiraS, Di TommasoA, NahmiasC (2011) ATIP, a novel superfamily of microtubule-associated proteins. Med Sci (Paris)27:244–246 https://doi.org/10.1051/medsci/2011273244
20	NicolosoMS, SpizzoR, ShimizuM, RossiS, CalinGA (2009) MicroRNAs–the micro steering wheel of tumour metastases. Nat Rev Cancer9:293–302 https://doi.org/10.1038/nrc2619
21	NouetS, AmzallagN, LiJM, LouisS, SeitzI, CuiTX, AlleaumeAM, Di BenedettoM, BodenC, MassonMet al. (2004) Transinactivation of receptor tyrosine kinases by novel angiotensin II AT2 receptor-interacting protein, ATIP. J Biol Chem279:28989–28997 https://doi.org/10.1074/jbc.M403880200
22	OliveV, LiQ, HeL (2013) mir-17-92: a polycistronic oncomir with pleiotropic functions. Immunol Rev253:158–166 https://doi.org/10.1111/imr.12054
23	RamalingamS, PawlishK, GadgeelS, DemersR, KalemkerianGP (1998) Lung cancer in young patients: analysis of a surveillance, epidemiology, and end results database. J Clin Oncol16:651–657 https://doi.org/10.1200/JCO.1998.16.2.651
24	RobainaMC, FaccionRS, MazzoccoliL, RezendeLM, QueirogaE, BacchiCE, Thomas-TikhonenkoA, KlumbCE (2016) miR-17-92 cluster components analysis in Burkitt lymphoma: overexpression of miR-17 is associated with poor prognosis. Ann Hematol95:881–891 https://doi.org/10.1007/s00277-016-2653-7
25	SeiboldS, RudroffC, WeberM, GalleJ, WannerC, MarxM (2003) Identification of a new tumor suppressor gene located at chromosome 8p21.3-22. FASEB J17:1180–1182 https://doi.org/10.1096/fj.02-0934fje
26	SiegelR, DeSantisC, VirgoK, SteinK, MariottoA, SmithT, CooperD, GanslerT, LerroC, FedewaSet al. (2012) Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin62:220–241 https://doi.org/10.3322/caac.21149
27	VarghayeeN, KrezelMA, RezmannL, ChowL, FraumanAG, LouisWJ, LouisSN (2015) Function and expression of ATIP and its variants in cardiomyoblast cell line H9c2. J Renin Angiotensin Aldosterone Syst16:79–91 https://doi.org/10.1177/1470320313483845
28	VelotL, MolinaA, Rodrigues-FerreiraS, NehligA, BouchetBP, MorelM, LeconteL, SerreL, ArnalI, BraguerDet al. (2015) Negative regulation of EB1 turnover at microtubule plus ends by interaction with microtubule-associated protein ATIP3. Oncotarget6:43557–43570
29	WangX, WangL, MoQ, JiaA, DongY, WangG (2016) A positive feedback loop of p53/miR-19/TP53INP1 modulates pancreatic cancer cell proliferation and apoptosis. Oncol Rep35:518–523
30	WruckCJ, Funke-KaiserH, PufeT, KusserowH, MenkM, SchefeJH, KruseML, StollM, UngerT (2005) Regulation of transport of the angiotensin AT2 receptor by a novel membrane-associated Golgi protein. Arterioscler Thromb Vasc Biol25:57–64
31	XiaoJ, ChenJX, ZhuYP, ZhouLY, ShuQA, ChenLW (2012) Reduced expression of MTUS1 mRNA is correlated with poor prognosis in bladder cancer. Oncol Lett4:113–118
32	YuJ, LiuX, YeH, ZhouX (2009) Genomic characterization of the human mitochondrial tumor suppressor gene 1 (MTUS1): 5’ cloning and preliminary analysis of the multiple gene promoters. BMC Res Notes2:109 https://doi.org/10.1186/1756-0500-2-109
33	ZhaoT, DingX, ChangB, ZhouX, WangA (2015) MTUS1/ATIP3a down-regulation is associated with enhanced migration, invasion and poor prognosis in salivary adenoid cystic carcinoma. BMC Cancer15:203 https://doi.org/10.1186/s12885-015-1209-x
34	ZuernC, HeimrichJ, KaufmannR, RichterKK, SettmacherU, WannerC, GalleJ, SeiboldS(2010) Down-regulation of MTUS1 in human colon tumors. Oncol Rep23:183–189

[1]

PAC-0455-16205-GYY_suppl_1

Download

[1]	Henry Y. Jiang, Sara Najmeh, Guy Martel, Elyse MacFadden-Murphy, Raquel Farias, Paul Savage, Arielle Leone, Lucie Roussel, Jonathan Cools-Lartigue, Stephen Gowing, Julie Berube, Betty Giannias, France Bourdeau, Carlos H. F. Chan, Jonathan D. Spicer, Rebecca McClure, Morag Park, Simon Rousseau, Lorenzo E. Ferri. Activation of the pattern recognition receptor NOD1 augments colon cancer metastasis[J]. Protein Cell, 2020, 11(3): 187-201.
[2]	Weiwei Jiang, Fangfang Cai, Huangru Xu, Yanyan Lu, Jia Chen, Jia Liu, Nini Cao, Xiangyu Zhang, Xiao Chen, Qilai Huang, Hongqin Zhuang, Zi-Chun Hua. Extracellular signal regulated kinase 5 promotes cell migration, invasion and lung metastasis in a FAK-dependent manner[J]. Protein Cell, 2020, 11(11): 825-845.
[3]	Xi Chen, Lin Wang, Rujin Huang, Hui Qiu, Peizhe Wang, Daren Wu, Yonglin Zhu, Jia Ming, Yangming Wang, Jianbin Wang, Jie Na. Dgcr8 deletion in the primitive heart uncovered novel microRNA regulating the balance of cardiac-vascular gene program[J]. Protein Cell, 2019, 10(5): 327-346.
[4]	Xiao-Shuai Han, Chen Wang, Fang-hao Guo, Shuang Huang, Yong-Wen Qin, Xian-Xian Zhao, Qing Jing. Neoblast-enriched zinc finger protein FIR1 triggers local proliferation during planarian regeneration[J]. Protein Cell, 2019, 10(1): 43-59.
[5]	Na Qu, Zhao Ma, Mengrao Zhang, Muaz N. Rushdi, Christopher J. Krueger, Antony K. Chen. Inhibition of retroviral Gag assembly by non-silencing miRNAs promotes autophagic viral degradation[J]. Protein Cell, 2018, 9(7): 640-651.
[6]	Xiaowei Chen, Zhen Fan, Warren McGee, Mengmeng Chen, Ruirui Kong, Pushuai Wen, Tengfei Xiao, Xiaomin Chen, Jianghong Liu, Li Zhu, Runsheng Chen, Jane Y. Wu. TDP-43 regulates cancer-associated microRNAs[J]. Protein Cell, 2018, 9(10): 848-866.
[7]	Jie Yang, Luming Zhao, Ming Xu, Na Xiong. Establishment and function of tissue-resident innate lymphoid cells in the skin[J]. Protein Cell, 2017, 8(7): 489-500.
[8]	Yingjiao Xue,Shenda Hou,Hongbin Ji,Xiangkun Han. Evolution from genetics to phenotype: reinterpretation of NSCLC plasticity, heterogeneity, and drug resistance[J]. Protein Cell, 2017, 8(3): 178-190.
[9]	Shaohong Chen, Guangxia Gao. MicroRNAs recruit eIF4E2 to repress translation of target mRNAs[J]. Protein Cell, 2017, 8(10): 750-761.
[10]	Jing-Peng Fu,Wei-Chuan Mo,Ying Liu,Perry F. Bartlett,Rong-Qiao He. Elimination of the geomagnetic field stimulates the proliferation of mouse neural progenitor and stem cells[J]. Protein Cell, 2016, 7(9): 624-637.
[11]	Kegan Zhu,Lei Liu,Junliang Zhang,Yanbo Wang,Hongwei Liang,Gentao Fan,Zhenhuan Jiang,Chen-Yu Zhang,Xi Chen,Guangxin Zhou. MiR-29b suppresses the proliferation and migration of osteosarcoma cells by targeting CDK6[J]. Protein Cell, 2016, 7(6): 434-444.
[12]	Zhiju Zhao,Shu Li,Erwei Song,Suling Liu. The roles of ncRNAs and histone-modifiers in regulating breast cancer stem cells[J]. Protein Cell, 2016, 7(2): 89-99.
[13]	Haiyang Zhang,Jingjing Duan,Yanjun Qu,Ting Deng,Rui Liu,Le Zhang,Ming Bai,Jialu Li,Tao Ning,Shaohua Ge,Xia Wang,Zhenzhen Wang,Qian Fan,Hongli Li,Guoguang Ying,Dingzhi Huang,Yi Ba. Onco-miR-24 regulates cell growth and apoptosis by targeting BCL2L11 in gastric cancer[J]. Protein Cell, 2016, 7(2): 141-151.
[14]	Qian Fan,Xiangrui Meng,Hongwei Liang,Huilai Zhang,Xianming Liu,Lanfang Li,Wei Li,Wu Sun,Haiyang Zhang,Ke Zen,Chen-Yu Zhang,Zhen Zhou,Xi Chen,Yi Ba. miR-10a inhibits cell proliferation and promotes cell apoptosis by targeting BCL6 in diffuse large B-cell lymphoma[J]. Protein Cell, 2016, 7(12): 899-912.
[15]	Chao Lu,Yang Yang,Ran Zhao,Bingxuan Hua,Chen Xu,Zuoqin Yan,Ning Sun,Ruizhe Qian. Role of circadian gene Clock during differentiation of mouse pluripotent stem cells[J]. Protein Cell, 2016, 7(11): 820-832.

Viewed

Full text

Abstract

Cited

Shared

Discussed