Long Non-coding RNA LINC02474 Affects Metastasis and Apoptosis of Colorectal Cancer by Inhibiting the Expression of GZMB

被引：20

作者：

Du, Tiantian ^{[1
]}

Gao, Qinglun ^{[2
]}

Zhao, Yinghui ^{[1
]}

Gao, Jie ^{[1
]}

Li, Juan ^{[1
]}

Wang, Lili ^{[3
]}

Li, Peilong ^{[1
]}

Wang, Yunshan ^{[1
]}

Du, Lutao ^{[1
,4
,5
]}

Wang, Chuanxin ^{[1
,4
,5
]}

机构：

[1] Shandong Univ, Cheeloo Coll Med, Hosp 2, Dept Clin Lab, Jinan, Peoples R China

[2] Shandong Univ, Cheeloo Coll Med, Shandong Prov Hosp 3, Dept Hepatobiliary Surg, Jinan, Peoples R China

[3] Shandong Univ, Qilu Hosp, Dept Clin Lab, Jinan, Peoples R China

[4] Shandong Univ, Hosp 2, Shandong Engn & Technol Res Ctr Tumor Marker Dete, Jinan, Peoples R China

[5] Shandong Univ, Hosp 2, Shandong Prov Clin Med Res Ctr Clin Lab, Jinan, Peoples R China

来源：

FRONTIERS IN ONCOLOGY | 2021年 / 11卷

基金：

中国国家自然科学基金;

关键词：

long non-coding RNA; colorectal cancer; migration; invasion; apoptosis; LNCRNA;

D O I：

10.3389/fonc.2021.651796

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Colorectal cancer (CRC) is one of the most frequently diagnosed malignancies. Metastasis is the main event that impedes the therapeutic effect on CRC, and its underlying mechanisms remain largely unclear. LINC02474 is a novel long noncoding RNA (lncRNA) associated with metastasis of CRC, while little is known about how LINC02474 regulates these malignant characteristics. Methods: Expressions of LINC02474 and granzyme B (GZMB) were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blotting analysis. Cell metastasis was detected by transwell assay and metastatic nude mouse model, and apoptosis was determined by Western blotting analysis and flow cytometry. Besides, the interaction between LINC02474 and GZMB was detected by dual-luciferase reporter assays. Results: The expression of LINC02474 was significantly up-regulated in CRC tissues. Moreover, depletion of LINC02474 damaged the metastatic abilities of CRC cells in vivo and in vitro while boosting apoptosis. Besides, up-regulation of LINC02474 could promote migration and invasion, while apoptosis was inhibited in CRC cells. Besides, down-regulation of LINC02474 promoted the expression of GZMB, and interference of GZMB could increase the metastatic abilities of CRC cells while reducing apoptosis. Furthermore, LINC02474 was related to the transcriptional repression of GZMB in CRC cells determined by the dual-luciferase reporter assay. Conclusions: The findings revealed that a novel lncRNA, LINC02474, as an oncogene, could promote metastasis, but limit apoptosis partly by impeding GZMB expression in CRC. Besides, LINC02474 had the potential to be used as a biomarker in the prognosis of CRC.

引用

页数：13

共 45 条

[1] Biomarkers in Colorectal Cancer: The Role of Translational Proteomics Research [J].

Alves Martins, Bruno Augusto ;

de Bulhoes, Gabriel Fonseca ;

Cavalcanti, Igor Norat ;

Martins, Mickaella Michelson ;

de Oliveira, Paulo Goncalves ;

Araujo Martins, Aline Maria .

FRONTIERS IN ONCOLOGY, 2019, 9

[2] A Micropeptide Encoded by a Putative Long Noncoding RNA Regulates Muscle Performance [J].

Anderson, Douglas M. ;

Anderson, Kelly M. ;

Chang, Chi-Lun ;

Makarewich, Catherine A. ;

Nelson, Benjamin R. ;

McAnally, John R. ;

Kasaragod, Prasad ;

Shelton, John M. ;

Liou, Jen ;

Bassel-Duby, Rhonda ;

Olson, Eric N. .

CELL, 2015, 160 (04) :595-606

[3] MULTIPROTEIN PARTICLES FROM T CELLS DELIVER CYTOTOXIC CARGO TO TARGETS [J].

不详 .

CANCER DISCOVERY, 2020, 10 (07) :899-899

[4] The Untold Story of Granzymes in Oncoimmunology: Novel Opportunities with Old Acquaintances [J].

Arias, Maykel ;

Martinez-Lostao, Luis ;

Santiago, Llipsy ;

Ferrandez, Angel ;

Granville, David J. ;

Pardo, Julian .

TRENDS IN CANCER, 2017, 3 (06) :407-422

[5] Long non-coding RNA SNGH7 Is activated by SP1 and exerts oncogenic properties by interacting with EZH2 in ovarian cancer [J].

Bai, Zhuanli ;

Wu, YinYing ;

Bai, Shuheng ;

Yan, Yanli ;

Kang, Haojing ;

Ma, Wen ;

Zhang, Jiangzhou ;

Gao, Ying ;

Hui, Beina ;

Ma, Hailin ;

Li, Rong ;

Zhang, Xiaozhi ;

Ren, Juan .

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2020, 24 (13) :7479-7489

[6] Pan-cancer analysis of whole genomes [J].

Campbell, Peter J. ;

Getz, Gad ;

Korbel, Jan O. ;

Stuart, Joshua M. ;

Jennings, Jennifer L. ;

Stein, Lincoln D. ;

Perry, Marc D. ;

Nahal-Bose, Hardeep K. ;

Ouellette, B. F. Francis ;

Li, Constance H. ;

Rheinbay, Esther ;

Nielsen, G. Petur ;

Sgroi, Dennis C. ;

Wu, Chin-Lee ;

Faquin, William C. ;

Deshpande, Vikram ;

Boutros, Paul C. ;

Lazar, Alexander J. ;

Hoadley, Katherine A. ;

Louis, David N. ;

Dursi, L. Jonathan ;

Yung, Christina K. ;

Bailey, Matthew H. ;

Saksena, Gordon ;

Raine, Keiran M. ;

Buchhalter, Ivo ;

Kleinheinz, Kortine ;

Schlesner, Matthias ;

Zhang, Junjun ;

Wang, Wenyi ;

Wheeler, David A. ;

Ding, Li ;

Simpson, Jared T. ;

O'Connor, Brian D. ;

Yakneen, Sergei ;

Ellrott, Kyle ;

Miyoshi, Naoki ;

Butler, Adam P. ;

Royo, Romina ;

Shorser, Solomon, I ;

Vazquez, Miguel ;

Rausch, Tobias ;

Tiao, Grace ;

Waszak, Sebastian M. ;

Rodriguez-Martin, Bernardo ;

Shringarpure, Suyash ;

Wu, Dai-Ying ;

Demidov, German M. ;

Delaneau, Olivier ;

Hayashi, Shuto .

NATURE, 2020, 578 (7793) :82-+

[7] The transcriptional landscape of the mammalian genome [J].

Carninci, P ;

Kasukawa, T ;

Katayama, S ;

Gough, J ;

Frith, MC ;

Maeda, N ;

Oyama, R ;

Ravasi, T ;

Lenhard, B ;

Wells, C ;

Kodzius, R ;

Shimokawa, K ;

Bajic, VB ;

Brenner, SE ;

Batalov, S ;

Forrest, ARR ;

Zavolan, M ;

Davis, MJ ;

Wilming, LG ;

Aidinis, V ;

Allen, JE ;

Ambesi-Impiombato, X ;

Apweiler, R ;

Aturaliya, RN ;

Bailey, TL ;

Bansal, M ;

Baxter, L ;

Beisel, KW ;

Bersano, T ;

Bono, H ;

Chalk, AM ;

Chiu, KP ;

Choudhary, V ;

Christoffels, A ;

Clutterbuck, DR ;

Crowe, ML ;

Dalla, E ;

Dalrymple, BP ;

de Bono, B ;

Della Gatta, G ;

di Bernardo, D ;

Down, T ;

Engstrom, P ;

Fagiolini, M ;

Faulkner, G ;

Fletcher, CF ;

Fukushima, T ;

Furuno, M ;

Futaki, S ;

Gariboldi, M .

SCIENCE, 2005, 309 (5740) :1559-1563

[8] A Long Noncoding RNA Controls Muscle Differentiation by Functioning as a Competing Endogenous RNA [J].

Cesana, Marcella ;

Cacchiarelli, Davide ;

Legnini, Ivano ;

Santini, Tiziana ;

Sthandier, Olga ;

Chinappi, Mauro ;

Tramontano, Anna ;

Bozzoni, Irene .

CELL, 2011, 147 (02) :358-369

[9] The Long Noncoding RNA CCAT2 Induces Chromosomal Instability Through BOP1-AURKB Signaling [J].

Chen, Baoqing ;

Dragomir, Mihnea P. ;

Fabris, Linda ;

Bayraktar, Recep ;

Knutsen, Erik ;

Liu, Xu ;

Tang, Changyan ;

Li, Yongfeng ;

Shimura, Tadanobu ;

Ivkovic, Tina Catela ;

De los Santos, Mireia Cruz ;

Anfossi, Simone ;

Shimizu, Masayoshi ;

Shah, Maitri Y. ;

Ling, Hui ;

Shen, Peng ;

Multani, Asha S. ;

Pardini, Barbara ;

Burks, Jared K. ;

Katayama, Hiroyuki ;

Reineke, Lucas C. ;

Huo, Longfei ;

Syed, Muddassir ;

Song, Shumei ;

Ferracin, Manuela ;

Oki, Eiji ;

Fromm, Bastian ;

Ivan, Cristina ;

Bhuvaneshwar, Krithika ;

Gusev, Yuriy ;

Mimori, Koshi ;

Menter, David ;

Sen, Subrata ;

Matsuyama, Takatoshi ;

Uetake, Hiroyuki ;

Vasilescu, Catalin ;

Kopetz, Scott ;

Parker-Thornburg, Jan ;

Taguchi, Ayumu ;

Hanash, Samir M. ;

Girnita, Leonard ;

Slaby, Ondrej ;

Goel, Ajay ;

Varani, Gabriele ;

Gagea, Mihai ;

Li, Chunlai ;

Ajani, Jaffer A. ;

Calin, George A. .

GASTROENTEROLOGY, 2020, 159 (06) :2146-2195

[10] Effect of Combined Immune Checkpoint Inhibition vs Best Supportive Care Alone in Patients With Advanced Colorectal Cancer The Canadian Cancer Trials Group CO.26 Study [J].

Chen, Eric X. ;

Jonker, Derek J. ;

Loree, Jonathan M. ;

Kennecke, Hagen F. ;

Berry, Scott R. ;

Couture, Felix ;

Ahmad, Chaudhary E. ;

Goffin, John R. ;

Kavan, Petr ;

Harb, Mohammed ;

Colwell, Bruce ;

Samimi, Setareh ;

Samson, Benoit ;

Abbas, Tahir ;

Aucoin, Nathalie ;

Aubin, Francine ;

Koski, Sheryl L. ;

Wei, Alice C. ;

Magoski, Nadine M. ;

Tu, Dongsheng ;

O'Callaghan, Chris J. .

JAMA ONCOLOGY, 2020, 6 (06) :831-838

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