HuR stabilizes lnc-Sox5 mRNA to promote tongue carcinogenesis
Tóm tắt
Long noncoding RNAs (lncRNAs) have been recently regarded as systemic regulators in multiple biological processes including tumorigenesis. In this study, we report an ultra-highly expressed lncRNA, lnc-Sox5, in tongue tumor tissues. The results imply that lnc-Sox5 may play vital role in tongue carcinoma progression. We observed that the growth of Tca8113 cells was suppressed by lnc-Sox5 downregulation. Additionally, lnc-Sox5 knockdown simultaneously increased Tca8113 cell apoptosis, but the cell cycle was arrested. RNA immunoprecipitation suggested that HuR directly bound to and stabilized lnc-Sox5 RNA. Consistently, HuR knockdown reduced the level of lnc-Sox5 in Tca8113 cells. However, overexpression of HuR induced more lnc-Sox5 in Tca8113 cells. Both lnc-Sox5 knockdown and HuR knockdown suppressed Tca8113 cell tumorigenesis in xenograft models. These results suggest that lnc-Sox5, which was stabilized by HuR, could regulate carcinogenesis of tongue cancer and may serve as a predicted target for tongue carcinoma therapies.
Tài liệu tham khảo
Siegel, R., Naishadham, D., and Jemal, A. (2012) Cancer statistics, CA Cancer J. Clin., 62, 10–29.
Jemal, A., Siegel, R., Ward, E., Murray, T., Xu, J., and Thun, M. J. (2007) Cancer statistics, CA Cancer J. Clin., 57, 43–66.
Nisar, Y. B. (2006) Association of smoking with lymph nodes metastasis in early stages of squamous cell carcinoma of tongue, J. Coll. Physicians Surg. Pak., 16, 312; author reply312.
Yamazaki, H., Inoue, T., Yoshida, K., Kotsuma, T., Yoshioka, Y., Koizumi, M., Furukawa, S., Kakimoto, N., Shimizutani, K., and Nishimura, T. (2009) Assessment of influence of smoking, drinking, leukoplakia and dental irritation on local control of early oral tongue carcinoma treated with brachytherapy: age and dental factors are potential prognostic factors, Tumori, 95, 461–466.
Sgaramella, N., Coates, P. J., Strindlund, K., Loljung, L., Colella, G., Laurell, G., Rossiello, R., Muzio, L. L., Loizou, C., Tartaro, G., Olofsson, K., Danielsson, K., Fahraeus, R., and Nylander, K. (2015) Expression of p16 in squamous cell carcinoma of the mobile tongue is independent of HPV infection despite presence of the HPV-receptor syndecan-1, British J. Cancer, 113, 321–326.
Zhang, H., Zhang, Y., Zhao, H., Niyaz, H., Liu, P., Zhang, L., Zhang, S., Reheman, Y., Bao, Y., and Chen, X. (2016) HPV infection and prognostic factors of tongue squamous cell carcinoma in different ethnic groups from geographically closed cohort in Xinjiang, China, Biochem. Res. Int., 7498706.
Diederichs, S. (2014) The four dimensions of noncoding RNA conservation, Trends Genet., 30, 121–123.
Liang, J., Liang, L., Ouyang, K., Li, Z., and Yi, X. (2016) MALAT1 induces tongue cancer cells’ EMT and inhibits apoptosis through Wnt/beta-catenin signaling pathway, J. Oral Pathol. Med., doi: 10.1111/jop.12466.
Zhang, H., Zhao, L., Wang, Y. X., Xi, M., Liu, S. L., and Luo, L. L. (2015) Long non-coding RNA HOTTIP is correlated with progression and prognosis in tongue squamous cell carcinoma, Tumor Biol. J. Int. Soc. Oncodev. Biol. Med., 36, 8805–8809.
Jia, L. F., Wei, S. B., Gan, Y. H., Guo, Y., Gong, K., Mitchelson, K., Cheng, J., and Yu, G. Y. (2014) Expression, regulation and roles of miR-26a and MEG3 in tongue squamous cell carcinoma, Int. J. Cancer, 135, 2282–2293.
Fang, Z., Wu, L., Wang, L., Yang, Y., Meng, Y., and Yang, H. (2014) Increased expression of the long non-coding RNA UCA1 in tongue squamous cell carcinomas: a possible correlation with cancer metastasis, Oral Surg. Oral Med. Oral Pathol. Oral Radiol., 117, 89–95.
Flippot, R., Malouf, G. G., Su, X., Mouawad, R., Spano, J. P., and Khayat, D. (2016) Cancer subtypes classification using long non-coding RNA, Oncotarget, doi: 10.18632/oncotarget.10213.
Xu, Q., Deng, F., Qin, Y., Zhao, Z., Wu, Z., Xing, Z., Ji, A., and Wang, Q. J. (2016) Long non-coding RNA regulation of epithelial-mesenchymal transition in cancer metastasis, Cell Death Dis., 7, e2254.
Li, Z., Zhao, L., and Wang, Q. (2016) Overexpression of long non-coding RNA HOTTIP increases chemoresistance of osteosarcoma cell by activating the Wnt/beta-catenin pathway, Am. J. Transl. Res., 8, 2385–2393.
Ma, W. J., Cheng, S., Campbell, C., Wright, A., and Furneaux, H. (1996) Cloning and characterization of HuR, a ubiquitously expressed Elav-like protein, J. Biol. Chem., 271, 8144–8151.
Chen, C. Y., and Shyu, A. B. (1995) AU-rich elements: characterization and importance in mRNA degradation, Trends Biochem. Sci., 20, 465–470.
Jacobson, A., and Peltz, S. W. (1996) Interrelationships of the pathways of mRNA decay and translation in eukaryotic cells, Annu. Rev. Biochem., 65, 693–739.
Grammatikakis, I., Abdelmohsen, K., and Gorospe, M. (2016) Posttranslational control of HuR function, Wiley Interdiscip. Rev. RNA, doi: 10.1002/wrna.1372.
Chai, Y., Liu, J., Zhang, Z., and Liu, L. (2016) HuR-regulated lncRNA NEAT1 stability in tumorigenesis and progression of ovarian cancer, Cancer Med., 5, 1588–1598.
Kim, J., Abdelmohsen, K., Yang, X., De, S., Grammatikakis, I., Noh, J. H., and Gorospe, M. (2016) LncRNA OIP5-AS1/cyrano sponges RNA-binding protein HuR, Nucleic Acids Res., 44, 2378–2392.
Noh, J. H., Kim, K. M., Abdelmohsen, K., Yoon, J. H., Panda, A. C., Munk, R., Kim, J., Curtis, J., Moad, C. A., Wohler, C. M., Indig, F. E., de Paula, W., Dudekula, D. B., De, S., Piao, Y., Yang, X., Martindale, J. L., De Cabo, R., and Gorospe, M. (2016) HuR and GRSF1 modulate the nuclear export and mitochondrial localization of the lncRNA RMRP, Genes Dev., 30, 1224–1239.