LncRNA PART1 modulates toll-like receptor pathways to influence cell proliferation and apoptosis in prostate cancer cells
Abstract
We investigated thoroughly the effect of lncRNA PART1 on prostate cancer cells proliferation and apoptosis, through regulating toll-like receptor (TLR) pathways. LncRNA PART1 expression was also examined by quantitative real-time polymerase chain reactions (qRT-PCR) in human tissues and the cells lines LNCaP and PC3. After transfection with si-PART1 or control constructs, the cell viability was measured by MTS and colony formation assays. In addition, the apoptosis rate of the prostate cancer cells was validated by TUNEL staining. Relationships between lncRNA PART1 expression and TLR pathway genes were demonstrated by qRT-PCR and Western blotting. High levels of lncRNA PART1 expression were correlated with advanced cancer stage and predication of poor survival. LncRNA PART1 levels was increased in PCa cells treated with 5α-dihydrotestosterone (DHT), confirming PART1 was directly induced by androgen. Moreover, down-regulation of lncRNA PART1 inhibited prostate cancer cell proliferation and accelerated cell apoptosis. In addition, lncRNA PART1 induced downstream genes expression in TLR pathways including TLR3, TNFSF10 and CXCL13 to further influence prostate cancer cells, indicating its carcinogenesis on prostate cancer. LncRNA PART1 promoted cell proliferation ability and apoptosis via the inhibition of TLR pathways in prostate cancer. LncRNA PART1 could hence be considered as a new target in the treatment of prostate cancer.
Acknowledgments
We would like to acknowledge the reviewers for their helpful comments on this paper.
References
Bi, M., Yu, H., Huang, B., and Tang, C. (2017). Long non-coding RNA PCAT-1 over-expression promotes proliferation and metastasis in gastric cancer cells through regulating CDKN1A. Gene 626, 337–343.10.1016/j.gene.2017.05.049Suche in Google Scholar PubMed
Chen, C.D., Welsbie, D.S., Tran, C., Baek, S.H., Chen, R., Vessella, R., Rosenfeld, M.G., and Sawyers, C.L. (2004). Molecular determinants of resistance to antiandrogen therapy. Nat. Med. 10, 33–39.10.1038/nm972Suche in Google Scholar PubMed
Farooqi, A.A., Bhatti, S., and Ismail, M. (2012a). TRAIL and vitamins: opting for keys to castle of cancer proteome instead of open sesame. Cancer Cell Int. 12, 22.10.1186/1475-2867-12-22Suche in Google Scholar PubMed PubMed Central
Farooqi, A.A., Rana, A., Riaz, A.M., Khan, A., Ali, M., Javed, S., Mukhtar, S., Minhaj, S., Rao, J.R., Rajpoot, J., et al. (2012b). NutriTRAILomics in prostate cancer: time to have two strings to one’s bow. Mol. Biol. Rep. 39, 4909–4914.10.1007/s11033-011-1286-0Suche in Google Scholar PubMed
Galli, R., Starace, D., Busa, R., Angelini, D.F., Paone, A., De Cesaris, P., Filippini, A., Sette, C., Battistini, L., Ziparo, E., et al. (2010). TLR stimulation of prostate tumor cells induces chemokine-mediated recruitment of specific immune cell types. J. Immunol. 184, 6658–6669.10.4049/jimmunol.0902401Suche in Google Scholar PubMed
Gan, S.S., Ye, J.Q., Wang, L., Qu, F.J., Chu, C.M., Tian, Y.J., Yang, W., and Cui, X.G. (2017). Inhibition of PCSK9 protects against radiation-induced damage of prostate cancer cells. Onco. Targets Ther. 10, 2139–2146.10.2147/OTT.S129413Suche in Google Scholar PubMed PubMed Central
Gonzalez-Reyes, S., Fernandez, J.M., Gonzalez, L.O., Aguirre, A., Suarez, A., Gonzalez, J.M., Escaff, S., and Vizoso, F.J. (2011). Study of TLR3, TLR4, and TLR9 in prostate carcinomas and their association with biochemical recurrence. Cancer Immunol. Immunother. 60, 217–226.10.1007/s00262-010-0931-0Suche in Google Scholar PubMed
Hanahan, D. and Weinberg, R.A. (2011). Hallmarks of cancer: the next generation. Cell 144, 646–674.10.1016/j.cell.2011.02.013Suche in Google Scholar PubMed
Hou, J., Aerts, J., den Hamer, B., van Ijcken, W., den Bakker, M., Riegman, P., van der Leest, C., van der Spek, P., Foekens, J.A., Hoogsteden, H.C., et al. (2010). Gene expression-based classification of non-small cell lung carcinomas and survival prediction. PLoS One 5, e10312.10.1371/journal.pone.0010312Suche in Google Scholar PubMed PubMed Central
Lemos, A.E., Ferreira, L.B., Batoreu, N.M., de Freitas, P.P., Bonamino, M.H., and Gimba, E.R. (2016). PCA3 long noncoding RNA modulates the expression of key cancer-related genes in LNCaP prostate cancer cells. Tumour Biol. 37, 11339–11348.10.1007/s13277-016-5012-3Suche in Google Scholar PubMed
Li, J., Yang, S., Su, N., Wang, Y., Yu, J., Qiu, H., He, X. (2016). Overexpression of long non-coding RNA HOTAIR leads to chemoresistance by activating the Wnt/beta-catenin pathway in human ovarian cancer. Tumour Biol. 37, 2057–2065.10.1007/s13277-015-3998-6Suche in Google Scholar PubMed
Lin, B., White, J.T., Ferguson, C., Bumgarner, R., Friedman, C., Trask, B., Ellis ,W., Lange, P., Hood, L., and Nelson, P.S. (2000). PART-1: a novel human prostate-specific, androgen-regulated gene that maps to chromosome 5q12. Cancer Res. 60, 858–863.Suche in Google Scholar
Luo, G., Wang, M., Wu, X., Tao, D., Xiao, X., Wang, L., Min, F., Zeng, F., and Jiang, G. (2015). Long non-coding RNA MEG3 inhibits cell proliferation and induces apoptosis in prostate cancer. Cell Physiol. Biochem. 37, 2209–2220.10.1159/000438577Suche in Google Scholar PubMed
Misawa, A., Takayama, K., Urano, T., and Inoue, S. (2016). Androgen-induced long noncoding RNA (lncRNA) SOCS2-AS1 promotes cell growth and inhibits apoptosis in prostate cancer cells. J. Biol. Chem. 291, 17861–17880.10.1074/jbc.M116.718536Suche in Google Scholar PubMed PubMed Central
Misawa, A., Takayama, K.I., Fujimura, T., Homma, Y., Suzuki, Y., and Inoue, S. (2017). Androgen-induced lncRNA POTEF-AS1 regulates apoptosis-related pathway to facilitate cell survival in prostate cancer cells. Cancer Sci. 108, 373–379.10.1111/cas.13151Suche in Google Scholar PubMed PubMed Central
Prensner, J.R., Rubin, M.A., Wei, J.T., and Chinnaiyan, A.M. (2012). Beyond PSA: the next generation of prostate cancer biomarkers. Sci. Transl. Med. 4, 127rv123.10.1126/scitranslmed.3003180Suche in Google Scholar PubMed PubMed Central
Prensner, J.R., Iyer, M.K., Sahu, A., Asangani, I.A., Cao, Q., Patel, L., Vergara, I.A., Davicioni, E., Erho, N., Ghadessi, M., et al. (2013). The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and antagonizes the SWI/SNF complex. Nat. Genet. 45, 1392–1398.10.1038/ng.2771Suche in Google Scholar PubMed PubMed Central
Sidiropoulos, M., Chang, A., Jung, K., and Diamandis, E.P. (2001). Expression and regulation of prostate androgen regulated transcript-1 (PART-1) and identification of differential expression in prostatic cancer. Br. J. Cancer. 85, 393–397.10.1054/bjoc.2001.1883Suche in Google Scholar PubMed PubMed Central
Takeda, K., Kaisho, T., and Akira, S. (2003). Toll-like receptors. Annu. Rev. Immunol. 21, 335–376.10.1146/annurev.immunol.21.120601.141126Suche in Google Scholar PubMed
Thomas, A.A., Pearce, A., Sharp, L., Gardiner, R.A., Chambers, S., Aitken, J., Molcho, M., and Baade, P. (2017). Socioeconomic disadvantage but not remoteness affects short-term survival in prostate cancer: a population-based study using competing risks. Asia Pac. J. Clin. Oncol. 13, e31–e40.10.1111/ajco.12570Suche in Google Scholar PubMed
Tosetti, V., Sassone, J., Ferri, A.L.M., Taiana, M., Bedini, G., Nava, S., Brenna, G., Di Resta, C., Pareyson, D., Di Giulio, A.M., et al. (2017). Transcriptional role of androgen receptor in the expression of long non-coding RNA Sox2OT in neurogenesis. PLoS One 12, e0180579.10.1371/journal.pone.0180579Suche in Google Scholar PubMed PubMed Central
Waltering, K.K., Helenius, M.A., Sahu, B., Manni, V., Linja, M.J., Janne, O.A., and Visakorpi, T. (2009). Increased expression of androgen receptor sensitizes prostate cancer cells to low levels of androgens. Cancer Res. 69, 8141–8149.10.1158/0008-5472.CAN-09-0919Suche in Google Scholar PubMed
Wang, H., Gao, X., Lu, X., Wang, Y., Ma, C., Shi, Z., Zhu, F., He, B., Xu, C., and Sun, Y. (2015). The mitotic regulator Hec1 is a critical modulator of prostate cancer through the long non-coding RNA BX647187 in vitro. Biosci Rep. 35, e00273.10.1042/BSR20150003Suche in Google Scholar PubMed PubMed Central
Wang, X., Ruan, Y., Wang, X., Zhao, W., Jiang, Q., Jiang, C., Zhao, Y., Xu, Y., Sun, F., Zhu, Y., et al. (2017). Long intragenic non-coding RNA lincRNA-p21 suppresses development of human prostate cancer. Cell Prolif. 50.10.1111/cpr.12318Suche in Google Scholar PubMed PubMed Central
Yu, L., Blackburn, G.L., and Zhou, J.R. (2003). Genistein and daidzein downregulate prostate androgen-regulated transcript-1 (PART-1) gene expression induced by dihydrotestosterone in human prostate LNCaP cancer cells. J. Nutr. 133, 389–392.10.1093/jn/133.2.389Suche in Google Scholar PubMed
Zhang, Y., Su, X., Kong, Z., Fu, F., Zhang, P., Wang, D., Wu, H., Wan, X., and Li, Y. (2017). An androgen reduced transcript of LncRNA GAS5 promoted prostate cancer proliferation. PLoS One 12, e0182305.10.1371/journal.pone.0182305Suche in Google Scholar PubMed PubMed Central
Zhao, S., Zhang, Y., Zhang, Q., Wang, F., and Zhang, D. (2014). Toll-like receptors and prostate cancer. Front. Immunol. 5, 352.10.3389/fimmu.2014.00352Suche in Google Scholar PubMed PubMed Central
Supplemental Material:
The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2017-0255).
©2018 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
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- Protein Structure and Function
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Artikel in diesem Heft
- Frontmatter
- Reviews
- Biomechanistic insights into the roles of oxidative stress in generating complex neurological disorders
- Metformin-induced anticancer activities: recent insights
- Research Articles/Short Communications
- Protein Structure and Function
- Interaction of the middle domains stabilizes Hsp90α dimer in a closed conformation with high affinity for p23
- How human serum albumin recognizes DNA and RNA
- In vitro reconstitution and biochemical characterization of human phospholipid scramblase 3: phospholipid specificity and metal ion binding studies
- Cell Biology and Signaling
- LncRNA KCNQ1OT1 ameliorates particle-induced osteolysis through inducing macrophage polarization by inhibiting miR-21a-5p
- LncRNA PART1 modulates toll-like receptor pathways to influence cell proliferation and apoptosis in prostate cancer cells
- High-content hydrogen water-induced downregulation of miR-136 alleviates non-alcoholic fatty liver disease by regulating Nrf2 via targeting MEG3