miR-7 Suppresses Tumor Progression by Directly Targeting MAP3K9 in Pancreatic Cancer.
miR-7 Suppresses Tumor Progression by Directly Targeting MAP3K9 in Pancreatic Cancer.
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miR-7 通过直接靶向胰腺癌中的 MAP3K9 来抑制肿瘤进展。
DOI：
10.1016/j.omtn.2018.08.012
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发表时间：
2018-12-07
期刊：
影响因子：
--
通讯作者：
Ma J
中科院分区：
文献类型：
--
作者：
Xia J;Cao T;Ma C;Shi Y;Sun Y;Wang ZP;Ma J
广泛的研究表明，miR-7在癌症进展中起着关键作用。然而，miR-7在胰腺癌（PC）进展中的生物学功能知之甚少。因此，本研究旨在探讨miR-7在PC进展中的作用及其分子机制。我们采用MTT法、流式细胞仪、Transwell法、RT-PCR、Western blotting和转染等方法研究miR-7在PC细胞中的作用。我们发现miR-7抑制PC细胞的生长、迁移和侵袭，但诱导PC细胞凋亡。此外，miR-7的过表达抑制了小鼠肿瘤的生长，表明miR-7可以在PC中发挥其肿瘤抑制功能。在机制上，我们证实了MAP 3 K9是miR-7的直接靶点，miR-7通过激活MEK/ERK通路和NF-κB通路显著促进PC细胞增殖并抑制细胞凋亡。此外，拯救实验还显示，miR-7通过直接靶向MAP 3 K9抑制PC细胞增殖并诱导PC细胞凋亡，导致MEK/ERK和NF-κB通路的抑制。综上所述，这些结果表明，miR-7/MAP 3 K9在PC进展中起关键作用，并且miR-7可能是PC治疗的潜在靶点。
Extensive research has suggested that miR-7 plays a critical role in cancer progression. However, the biological function of miR-7 in pancreatic cancer (PC) progression is poorly understood. Therefore, in the present study, we investigated the function of miR-7 and its molecular mechanism in PC progression. We used multiple methods, such as MTT, FACS, Transwell assay, RT-PCR, western blotting, and transfection to investigate the role of miR-7 in PC cells. We found that miR-7 suppressed cell growth, migration, and invasion but induced apoptosis in PC cells. Moreover, overexpression of miR-7 repressed tumor growth in mice, suggesting that miR-7 could exert its tumor-suppressive function in PC. Mechanistically, we validated that MAP3K9 is a direct target of miR-7, which significantly enhanced PC cell proliferation and inhibited cell apoptosis partly through activation of the MEK/ERK pathway and NF-κB pathway. Moreover, rescue experiments also showed that miR-7 suppressed PC cell proliferation and induced PC cell apoptosis by directly targeting MAP3K9, leading to inhibition of the MEK/ERK and NF-κB pathways. Taken together, these results suggest that miR-7/MAP3K9 is critically involved in PC progression and that miR-7 may be a potential target for PC treatment.
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影响因子：
6.4
作者：
Pothoulakis C;Torre-Rojas M;Duran-Padilla MA;Gevorkian J;Zoras O;Chrysos E;Chalkiadakis G;Baritaki S
通讯作者：
Baritaki S
影响因子：
30.8
作者：
Stark, Mitchell S.;Woods, Susan L.;Gartside, Michael G.;Bonazzi, Vanessa F.;Dutton-Regester, Ken;Aoude, Lauren G.;Chow, Donald;Sereduk, Chris;Niemi, Natalie M.;Tang, Nanyun;Ellis, Jonathan J.;Reid, Jeffrey;Zismann, Victoria;Tyagi, Sonika;Muzny, Donna;Newsham, Irene;Wu, YuanQing;Palmer, Jane M.;Pollak, Thomas;Youngkin, David;Brooks, Bradford R.;Lanagan, Catherine;Schmidt, Christopher W.;Kobe, Bostjan;MacKeigan, Jeffrey P.;Yin, Hongwei;Brown, Kevin M.;Gibbs, Richard;Trent, Jeffrey;Hayward, Nicholas K.
通讯作者：
Hayward, Nicholas K.
影响因子：
5.4
作者：
Bi Y;Shen W;Min M;Liu Y
通讯作者：
Liu Y
影响因子：
16.6
作者：
Marusiak, Anna A.;Edwards, Zoe C.;Hugo, Willy;Trotter, Eleanor W.;Girotti, Maria R.;Stephenson, Natalie L.;Kong, Xiangju;Gartside, Michael G.;Fawdar, Shameem;Hudson, Andrew;Breitwieser, Wolfgang;Hayward, Nicholas K.;Marais, Richard;Lo, Roger S.;Brognard, John
通讯作者：
Brognard, John
DOI：
10.1158/1078-0432.ccr-16-0720
发表时间：
2017-01-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Kang H;Tan M;Bishop JA;Jones S;Sausen M;Ha PK;Agrawal N
通讯作者：
Agrawal N