Long non-coding RNA THOR promotes ovarian Cancer cells progression via IL-6/STAT3 pathway

被引:22
作者
Ge, Jing [1 ,2 ]
Han, Tao [1 ,3 ]
Shan, Lili [1 ,2 ]
Na, Jing [1 ,2 ]
Li, Ya [1 ,2 ]
Wang, Jun [1 ,2 ]
机构
[1] Dalian Med Univ, Affiliated Hosp 2, Dept Gynecol & Obstet, Dalian 116023, Liaoning, Peoples R China
[2] Gen Hosp Northern Theater Command, Dept Gynecol & Obstet, Shenyang 110016, Liaoning, Peoples R China
[3] Gen Hosp Northern Theater Command, Dept Oncol, Shenyang 110016, Liaoning, Peoples R China
基金
中国博士后科学基金;
关键词
Ovarian cancer; THOR; IL-6; STAT3; Progression; Prognosis; IL-6/JAK/STAT3; PATHWAY; STEM-CELLS; SUPPRESSES; EXPRESSION; THERAPY; RISK; P53;
D O I
10.1186/s13048-020-00672-1
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background Ovarian cancer (OC) is one of the most common malignant tumors in the world. The prognosis of OC remains poor due to the advanced stage and distant metastasis at the time of diagnosis. Recently, a novel lncRNA, THOR (testis-associated highly conserved oncogenic long non-coding RNA), was characterized in human cancers and shown to exhibit an oncogenic role. However, the role of THOR in OC remains unclear. Methods RT-PCR and western blot analysis were used to detect the expression of THOR, p-STAT3 and IL-6. The impact of THOR on OC proliferation, metastasis and self-renewal was investigated in vitro and in vivo. The prognostic value of THOR was determined in OC patient cohorts. Results In this study, our results find that THOR is markedly upregulated in human OC tissues and predicts the poor prognosis of OC patients. Functional studies have revealed that knockdown of THOR inhibits the growth, metastasis and self-renewal of OC cells. Mechanistically, THOR drives OC cell progression via the IL-6/STAT3 signaling. Moreover, the specific STAT3 inhibitor S3I-201 or IL-6R inhibitor tocilizumab diminish the discrepancy in the growth, metastatic and self-renewal capacity between THOR-silenced OC cells and control cells, which further confirm that IL-6/STAT3 is required in THOR-driven OC cells progression. Conclusion Our findings reveal that THOR could promote OC cells growth, metastasis and self-renewal by activating IL-6/STAT3 signaling and may be a good predictive factor and therapeutic target.
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页数:11
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共 37 条
[1]   Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer [J].
Bowtell, David D. ;
Boehm, Steffen ;
Ahmed, Ahmed A. ;
Aspuria, Paul-Joseph ;
Bast, Robert C., Jr. ;
Beral, Valerie ;
Berek, Jonathan S. ;
Birrer, Michael J. ;
Blagden, Sarah ;
Bookman, Michael A. ;
Brenton, James D. ;
Chiappinelli, Katherine B. ;
Martins, Filipe Correia ;
Coukos, George ;
Drapkin, Ronny ;
Edmondson, Richard ;
Fotopoulou, Christina ;
Gabra, Hani ;
Galon, Jerome ;
Gourley, Charlie ;
Heong, Valerie ;
Huntsman, David G. ;
Iwanicki, Marcin ;
Karlan, Beth Y. ;
Kaye, Allyson ;
Lengyel, Ernst ;
Levine, Douglas A. ;
Lu, Karen H. ;
McNeish, Iain A. ;
Menon, Usha ;
Narod, Steven A. ;
Nelson, Brad H. ;
Nephew, Kenneth P. ;
Pharoah, Paul ;
Powell, Daniel J., Jr. ;
Ramos, Pilar ;
Romero, Iris L. ;
Scott, Clare L. ;
Sood, Anil K. ;
Stronach, Euan A. ;
Balkwill, Frances R. .
NATURE REVIEWS CANCER, 2015, 15 (11) :668-679
[2]   miR-214 activates TP53 but suppresses the expression of RELA, CTNNB1, and STAT3 in human cervical and colorectal cancer cells [J].
Chandrasekaran, Karthik Subramanian ;
Sathyanarayanan, Anusha ;
Karunagaran, Devarajan .
CELL BIOCHEMISTRY AND FUNCTION, 2017, 35 (07) :464-471
[3]   Secretory RAB GTPase 3C modulates IL6-STAT3 pathway to promote colon cancer metastasis and is associated with poor prognosis [J].
Chang, Yu-Chan ;
Su, Chia-Yi ;
Chen, Ming-Huang ;
Chen, Wei-Shone ;
Chen, Chi-Long ;
Hsiao, Michael .
MOLECULAR CANCER, 2017, 16
[4]   Cancer Statistics in China, 2015 [J].
Chen, Wanqing ;
Zheng, Rongshou ;
Baade, Peter D. ;
Zhang, Siwei ;
Zeng, Hongmei ;
Bray, Freddie ;
Jemal, Ahmedin ;
Yu, Xue Qin ;
He, Jie .
CA-A CANCER JOURNAL FOR CLINICIANS, 2016, 66 (02) :115-132
[5]   Long non-coding RNA THOR promotes cell proliferation and metastasis in hepatocellular carcinoma [J].
Cheng, Zhangjun ;
Lei, Zhengqing ;
Yang, Pinghua ;
Si, Anfeng ;
Xiang, Daimin ;
Zhou, Jiahua ;
Hueser, Norbert .
GENE, 2018, 678 :129-136
[6]   Low Grade Serous Ovarian Carcinoma: From the molecular characterization to the best therapeutic strategy [J].
Della Pepa, Chiara ;
Tonini, Giuseppe ;
Santini, Daniele ;
Losito, Simona ;
Pisano, Carmela ;
Di Napoli, Marilena ;
Cecere, Sabrina Chiara ;
Gargiulo, Piera ;
Pignata, Sandro .
CANCER TREATMENT REVIEWS, 2015, 41 (02) :136-143
[7]   Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of β-secretase [J].
Faghihi, Mohammad Ali ;
Modarresi, Farzaneh ;
Khalil, Ahmad M. ;
Wood, Douglas E. ;
Sahagan, Barbara G. ;
Morgan, Todd E. ;
Finch, Caleb E. ;
Laurent, Georges St., III ;
Kenny, Paul J. ;
Wahlestedt, Claes .
NATURE MEDICINE, 2008, 14 (07) :723-730
[8]   RNA in unexpected places: long non-coding RNA functions in diverse cellular contexts [J].
Geisler, Sarah ;
Coller, Jeff .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2013, 14 (11) :699-712
[9]   Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis [J].
Gupta, Rajnish A. ;
Shah, Nilay ;
Wang, Kevin C. ;
Kim, Jeewon ;
Horlings, Hugo M. ;
Wong, David J. ;
Tsai, Miao-Chih ;
Hung, Tiffany ;
Argani, Pedram ;
Rinn, John L. ;
Wang, Yulei ;
Brzoska, Pius ;
Kong, Benjamin ;
Li, Rui ;
West, Robert B. ;
van de Vijver, Marc J. ;
Sukumar, Saraswati ;
Chang, Howard Y. .
NATURE, 2010, 464 (7291) :1071-U148
[10]   Modular regulatory principles of large non-coding RNAs [J].
Guttman, Mitchell ;
Rinn, John L. .
NATURE, 2012, 482 (7385) :339-346