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

Yuanyuan Gu , Shuoxin Liu , Xiaodan Zhang , Guimin Chen , Hongwei Liang , Mengchao Yu , Zhicong Liao , Yong Zhou , Chen-Yu Zhang , Tao Wang , Chen Wang , Junfeng Zhang , Xi Chen

Protein Cell ›› 2017, Vol. 8 ›› Issue (6) : 455 -466.

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Protein Cell ›› 2017, Vol. 8 ›› Issue (6) : 455 -466. DOI: 10.1007/s13238-017-0393-7
RESEARCH ARTICLE
RESEARCH ARTICLE

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

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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

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Yuanyuan Gu, Shuoxin Liu, Xiaodan Zhang, Guimin Chen, Hongwei Liang, Mengchao Yu, Zhicong Liao, Yong Zhou, Chen-Yu Zhang, Tao Wang, Chen Wang, Junfeng Zhang, Xi Chen. Oncogenic miR-19a and miR-19b co-regulate tumor suppressor MTUS1 to promote cell proliferation and migration in lung cancer. Protein Cell, 2017, 8(6): 455-466 DOI:10.1007/s13238-017-0393-7

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References

[1]

AdamsBD, KasinskiAL, SlackFJ (2014) Aberrant regulation and function of microRNAs in cancer. Curr Biol24:R762–R776

[2]

AmbrosV (2004) The functions of animal microRNAs. Nature431:350–355

[3]

BartelDP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell116:281–297

[4]

CalinGA, CroceCM (2006) MicroRNA signatures in human cancers. Nat Rev Cancer6:857–866

[5]

Di BenedettoM, BiecheI, DeshayesF, VacherS, NouetS, ColluraV, SeitzI, LouisS, PineauP, Amsellem-OuazanaD (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

[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

[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

[9]

HeL, HannonGJ (2004) MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet5:522–531

[10]

KangSM, LeeHJ (2014) MicroRNAs in human lung cancer. Exp Biol Med (Maywood)239:1505–1513

[11]

KinjoT, IsomuraM, IwamasaT, NakamuraY (2000)Molecular cloning and characterization of two novel genes on chromosome 8p21.3. J Hum Genet45:12–17

[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

[13]

LiX, LiuH, YuT, DongZ, TangL, SunX (2014a) Loss of MTUS1 in gastric cancer promotes tumor growth and metastasis. Neoplasma61:128–135

[14]

LiX, XieW, XieC, HuangC, ZhuJ, LiangZ, DengF, ZhuM, ZhuW, WuR (2014b) Curcumin modulates miR-19/PTEN/AKT/p53 axis to suppress bisphenol A-induced MCF-7 breast cancer cell proliferation. Phytother Res28:1553–1560

[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

[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

[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

[19]

MolinaA, Rodrigues-FerreiraS, Di TommasoA, NahmiasC (2011) ATIP, a novel superfamily of microtubule-associated proteins. Med Sci (Paris)27:244–246

[20]

NicolosoMS, SpizzoR, ShimizuM, RossiS, CalinGA (2009) MicroRNAs–the micro steering wheel of tumour metastases. Nat Rev Cancer9:293–302

[21]

NouetS, AmzallagN, LiJM, LouisS, SeitzI, CuiTX, AlleaumeAM, Di BenedettoM, BodenC, MassonM (2004) Transinactivation of receptor tyrosine kinases by novel angiotensin II AT2 receptor-interacting protein, ATIP. J Biol Chem279:28989–28997

[22]

OliveV, LiQ, HeL (2013) mir-17-92: a polycistronic oncomir with pleiotropic functions. Immunol Rev253:158–166

[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

[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

[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

[26]

SiegelR, DeSantisC, VirgoK, SteinK, MariottoA, SmithT, CooperD, GanslerT, LerroC, FedewaS (2012) Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin62:220–241

[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

[28]

VelotL, MolinaA, Rodrigues-FerreiraS, NehligA, BouchetBP, MorelM, LeconteL, SerreL, ArnalI, BraguerD (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

[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

[34]

ZuernC, HeimrichJ, KaufmannR, RichterKK, SettmacherU, WannerC, GalleJ, SeiboldS(2010) Down-regulation of MTUS1 in human colon tumors. Oncol Rep23:183–189

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