Exosomal lncRNA 91H is associated with poor development in colorectal cancer by modifying HNRNPK expression

Cancer Cell International - Tập 18 - Trang 1-10 - 2018
Tianyi Gao1, Xiangxiang Liu2, Bangshun He2, Zhenlin Nie1, Chengbin Zhu1, Pei Zhang1, Shukui Wang1,2
1Department of clinical Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
2Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, China

Tóm tắt

Exosomes mediated transfer of lncRNA 91H may play a critical role in the development of CRC. However, few studies have proved the mechanism. So we performed this study to deeply explore the biological functions of exosomal 91H in the development and progression of CRC. The association between lncRNA 91H and exosomes was detected in vitro and vivo. Then RNA pulldown and RIP were used to detect how lncRNA 91H affect CRC IGF2 express. At last, clinic pathological significance of exosomal 91H was evaluated by Cox proportional hazards model. We found that serum lncRNA 91H expression was closely related to cancer exosomes in vitro and vivo which may enhance tumor-cell migration and invasion in tumor development by modifying HNRNPK expression. Then the clinic pathological significance of exosomal 91H was evaluated which demonstrated that CRC patients with high lncRNA 91H expression usually showed a higher risk in tumor recurrence and metastasis than patients with low lncRNA 91H expression (P < 0.05). All these data suggested that exosomal lncRNA 91H enhancing CRC metastasis by modifying HNRNPK expression might be an early plasma-based biomarker for CRC recurrence or metastasis. Further large-scale studies are needed to confirm our findings.

Tài liệu tham khảo

Kolligs FT. Diagnostics and epidemiology of colorectal cancer. Visc Med. 2016;32:158–64. https://doi.org/10.1159/000446488. Edwards BK, Noone AM, Mariotto AB, Simard EP, Boscoe FP, Henley SJ, Jemal A, Cho H, Anderson RN, Kohler BA, Eheman CR, Ward EM. Annual report to the nation on the status of cancer, 1975–2010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer. Cancer. 2014;120:1290–314. Zheng Y, Yang C, Tong S, Ding Y, Deng W, Song D, Xiao K. Genetic variation of long non-coding RNA TINCR contribute to the susceptibility and progression of colorectal cancer. Oncotarget. 2017;8:33536. Nissan A, Stojadinovic A, Mitrani-Rosenbaum S, Halle D, Grinbaum R, Roistacher M, Bochem A, Dayanc BE, Ritter G, Gomceli I, Bostanci EB, Akoglu M, Chen YT, Old LJ, Gure AO. Colon cancer associated transcript-1: a novel RNA expressed in malignant and pre-malignant human tissues. Int J Cancer. 2012;130:1598–606. Takahashi Y, Sawada G, Kurashige J, Uchi R, Matsumura T, Ueo H, Takano Y, Eguchi H, Sudo T, Sugimachi K, Yamamoto H, Doki Y, Mori M, Mimori K. Amplification of PVT-1 is involved in poor prognosis via apoptosis inhibition in colorectal cancers. Br J Cancer. 2014;110:164–71. Zheng HT, Shi DB, Wang YW, Li XX, Xu Y, Tripathi P, Gu WL, Cai GX, Cai SJ. High expression of lncRNA MALAT1 suggests a biomarker of poor prognosis in colorectal cancer. Int J Clin Exp Pathol. 2014;7:3174–81. Deng Q, He B, Gao T, Pan Y, Sun H, Xu Y, Li R, Ying H, Wang F, Liu X, Chen J, Wang S. Up-regulation of lncRNA 91H promotes tumor metastasis and predicts poor prognosis for patients with colorectal cancer. PLoS ONE. 2014;9(7):e103022. Xia WK, Lin QF, Shen D, Liu ZL, Su J, Mao WD. Clinical implication of long noncoding RNA lncRNA 91H expression profile in osteosarcoma patients. Onco Targets Ther. 2016;9:4645–52. Berteaux N, Aptel N, Cathala G, Genton C, Coll J, Daccache A, Spruyt N, Hondermarck H, Dugimont T, Curgy JJ, Forné T, Adriaenssens E. A novel H19 antisense RNA overexpressed in breast cancer contributes to paternal IGF2 expression. Mol Cell Biol. 2008;28(22):6731–45. Ostenfeld MS, Jeppesen DK, Laurberg JR, Boysen AT, Bramsen JB, Primdal-Bengtson B, et al. Cellu lar disposal of miR23b by RAB27-dependent exosome release is linked to acquisition of metastatic properties. Cancer Res. 2014;74:5758–71. Takahashi K, Yan IK, Kogure T, Haga H, Patel T. Extracellular vesicle-mediated transfer of long non coding RNA ROR modulates chemosensitivity in human hepatocellular cancer. FEBS Open Bio. 2014;4:458–67. Laurent LC, Abdel-Mageed AB, Adelson PD, Arango J, Balaj L, Breakefield X, Carlson E, Carter BS, Majem B, Chen CC, Cocucci E, Danielson K, Courtright A, et al. Meeting report: discussions and preliminary findings on extracellular RNA measurement methods from laboratories in the NIH Extracellular RNA Communication Consortium. J Extracell Vesicles. 2015;4:26533. Enderle D, Spiel A, Coticchia CM, Berghoff E, Mueller R, Schlumpberger M, Sprenger-Haussels M, Shaffer JM, Lader E, Skog J, Noerholm M. Characterization of RNA from exosomes and other extracellular vesicles isolated by a novel spin column-based method. PLoS ONE. 2015;10:e0136133. Steinbichler TB, Dudás J, Riechelmann H, Skvortsova II. The role of exosomes in cancer metastasis. Semin Cancer Biol. 2017;44:170–81. Pan L, Liang W, Fu M, Huang ZH, Li X, Zhang W, Zhang P, Qian H, Jiang PC, Xu WR, Zhang X. Exosomes-mediated transfer of long noncoding RNA ZFAS1 promotes gastric cancer progression. J Cancer Res Clin Oncol. 2017;143:991–1004. Berrondo C, Flax J, Kucherov V, Siebert A, Osinski T, Rosenberg A, Fucile C, Richheimer S, Beckham CJ. Expression of the long non-coding RNA HOTAIR correlates with disease progression in bladder cancer and is contained in bladder cancer patient urinary exosomes. PLoS ONE. 2016;11(1):e0147236. Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature. 2001;411:494–8. Hewson C, Morris KV. Form and function of exosome-associated long non-coding RNAs in cancer. Curr Top Microbiol Immunol. 2016;394:41–56. Thery C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol. 2002;2:569–79. Lee Y, El Andaloussi S, Wood MJ. Exosomes and microvesicles: extracellular vesicles for genetic information transfer and gene therapy. Hum Mol Genet. 2012;21:R125–34. Ramteke A, Ting H, Agarwal C, Mateen S, Somasagara R, Hussain A, Graner M, Frederick B, Agarwal R, Deep G. Exosomes secreted under hypoxia enhance invasiveness and stemness of prostate tumor cells by targeting adherens junction molecules. Mol Carcinog. 2015;54(7):554–65. Mu W, Rana S, Zöller M. Host matrix modulation by cancer exosomes promotes motility and invasiveness. Neoplasia. 2013;15(8):875–87. Greening DW, Gopal SK, Mathias RA, Liu L, Sheng J, Zhu HJ, Simpson RJ. Emerging roles of exosomes during epithelial–mesenchymal transition and cancer progression. Sem Cell Dev Biol. 2015;40:60–71. Klimek-Tomczak K, Mikula M, Dzwonek A, Paziewska A, Karczmarski J, Hennig E, Bujnicki JM, Bragoszewski P, Denisenko O, Bomsztyk K, Ostrowski J. Editing of hnRNP K protein mRNA in colorectal adenocarcinoma and surrounding mucosa. Br J Cancer. 2006;94(4):586–92. Roychoudhury P, Chaudhuri K. Evidence for heterogeneous nuclear ribonucleoprotein K overexpression in oral squamous cell carcinoma. Br J Cancer. 2007;97(4):574–5. Inoue A, Sawata SY, Taira K, Wadhwa R. Loss-of-function screening by randomized intracellular antibodies: identification of hnRNP-K as a potential target for metastasis. Proc Natl Acad Sci USA. 2007;104(21):8983–8.