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

PDF(1586 KB)
PDF(1586 KB)
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

Author information +
History +

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

Cite this article

Download citation ▾
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 https://doi.org/10.1007/s13238-017-0393-7

References

[1]
AdamsBD, KasinskiAL, SlackFJ (2014) Aberrant regulation and function of microRNAs in cancer. Curr Biol24:R762–R776
CrossRef Google scholar
[2]
AmbrosV (2004) The functions of animal microRNAs. Nature431:350–355
CrossRef Google scholar
[3]
BartelDP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell116:281–297
CrossRef Google scholar
[4]
CalinGA, CroceCM (2006) MicroRNA signatures in human cancers. Nat Rev Cancer6:857–866
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[9]
HeL, HannonGJ (2004) MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet5:522–531
CrossRef Google scholar
[10]
KangSM, LeeHJ (2014) MicroRNAs in human lung cancer. Exp Biol Med (Maywood)239:1505–1513
CrossRef Google scholar
[11]
KinjoT, IsomuraM, IwamasaT, NakamuraY (2000)Molecular cloning and characterization of two novel genes on chromosome 8p21.3. J Hum Genet45:12–17
CrossRef Google scholar
[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
CrossRef Google scholar
[13]
LiX, LiuH, YuT, DongZ, TangL, SunX (2014a) Loss of MTUS1 in gastric cancer promotes tumor growth and metastasis. Neoplasma61:128–135
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[19]
MolinaA, Rodrigues-FerreiraS, Di TommasoA, NahmiasC (2011) ATIP, a novel superfamily of microtubule-associated proteins. Med Sci (Paris)27:244–246
CrossRef Google scholar
[20]
NicolosoMS, SpizzoR, ShimizuM, RossiS, CalinGA (2009) MicroRNAs–the micro steering wheel of tumour metastases. Nat Rev Cancer9:293–302
CrossRef Google scholar
[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
CrossRef Google scholar
[22]
OliveV, LiQ, HeL (2013) mir-17-92: a polycistronic oncomir with pleiotropic functions. Immunol Rev253:158–166
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[26]
SiegelR, DeSantisC, VirgoK, SteinK, MariottoA, SmithT, CooperD, GanslerT, LerroC, FedewaS (2012) Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin62:220–241
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[34]
ZuernC, HeimrichJ, KaufmannR, RichterKK, SettmacherU, WannerC, GalleJ, SeiboldS(2010) Down-regulation of MTUS1 in human colon tumors. Oncol Rep23:183–189

RIGHTS & PERMISSIONS

2017 The Author(s) 2017. This article is an open access publication
AI Summary AI Mindmap
PDF(1586 KB)

Accesses

Citations

Detail

Sections
Recommended

/