- Email: [email protected]
Response to “Circular RNA profile identifies circPVT1 as a proliferative factor and prognostic marker in gastric cancer,” Cancer Lett. 2017 Mar 1; 388(2017): 208–219
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Cancer Letters xxx (2017) 1e2
Contents lists available at ScienceDirect
Cancer Letters journal homepage: www.elsevier.com/locate/canlet
Commentaries
Q3
Response to “Circular RNA profile identifies circPVT1 as a proliferative factor and prognostic marker in gastric cancer,” Cancer Lett. 2017 Mar 1; 388(2017): 208e219
Q2
Yan Li a, b, Shenglin Huang a, b, * a b
Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
a r t i c l e i n f o Article history: Received 11 May 2017 Accepted 13 May 2017 Keywords: Gastric cancer Circular RNA Proliferation Prognosis
Dear Editor, We much appreciated for the comment on our manuscript [1]. However, there are some misunderstanding in this comment. Firstly, the authors concluded that circPVT1 played a cancer suppressor role in vivo (from the clinical correlation), while was proved to act an oncogene in vitro (from the functional assays). However, the clinical correlation (biomarker) may have no functional implication. We were also very curious about the contradiction between clinical implication and cellular function of circPVT1 in GC. Indeed, we observed similar results in liver cancer (unpublished data). Secondly, the authors claimed that only one study reported the effect of circPVT1 in the past [2]. But this paper published in 2006 did not mention anything about circPVT1 or circRNA. In fact, a most recent paper published in Nucleic Acids Research and reported that circPVT1, elevated in dividing cells and reduced in senescent cells, sequesters let-7 to enable a proliferative phenotype [3]. This function is consistent with our result in GC cells. Thirdly, although we first characterized the circular RNA profile of GC from three paried GC tissues, the expression of circPVT1 was further validated from about 200 patients (Fig. 3A). We used ROC curves to compare
the prognosis of circPVT1 expression, TNM stage and tumor size, all of which are independent prognostic factors. AUC level is relatively low because this analysis is not for diagnosis. We also analyzed the TCGA clinical data, and found similar or lower AUC level. Fourthly, the author claimed that sequence binding between circular RNA and microRNA is usually seven consecutive base complementation pairing at least. However, there are only several papers (including our recent paper published in Nature communications [4]) reported the association of circRNA and miRNA, and the feature about base complementation pairing between circRNA and miRNA remains to be explored. Also sequence binding between miRNA and mRNA is not always seven consecutive base complementation pairing (8mer,7mer-m8 and 7mer-1A). Finally, we found that silencing of circPVT1 inhibits the proliferation of gastric cancer cells and circPVT1 serves as a miRNA sponge for the miR-125 family. The preliminary function and molecular mechanism of circPVT1 was explored in gastric cancer cells. Thanks for the suggestion to detect the detailed molecule indicators of cell proliferation by western blot and flow cytometry. In addition, PVT1 was primarily localized within the nucleus in AGS and MGC-803 cells, because we analysed the localization of PVT1 in AGS (Fig. 2C), MGC-803 (Supplementary Fig. S3A) and HEK-293T cells (data not shown) and found that more than 50% of PVT1 localized in the nucleus in all these three cells (AGS 50%, MGC-803 61%, and HEK-293T 71%). Conflict of interest The author declares no conflict of interest. References [1] J. Chen, Y. Li, Q. Zheng, C. Bao, J. He, B. Chen, et al., Circular RNA profile identifies circPVT1 as a proliferative factor and prognostic marker in gastric cancer, Cancer Lett. 388 (2017) 208e219.
DOI of original article: http://dx.doi.org/10.1016/j.canlet.2017.05.009. * Corresponding author. Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China. E-mail address: [email protected] (S. Huang). http://dx.doi.org/10.1016/j.canlet.2017.05.008 0304-3835/© 2017 Elsevier B.V. All rights reserved.
Please cite this article in press as: Y. Li, S. Huang, Response to “Circular RNA profile identifies circPVT1 as a proliferative factor and prognostic marker in gastric cancer,” Cancer Lett. 2017 Mar 1; 388(2017): 208e219, Cancer Letters (2017), http://dx.doi.org/10.1016/j.canlet.2017.05.008
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Y. Li, S. Huang / Cancer Letters xxx (2017) 1e2
[2] G.P. Dillon, T. Feltwell, J.P. Skelton, P.D. Ashton, P.S. Coulson, M.A. Quail, et al., Microarray analysis identifies genes preferentially expressed in the lung schistosomulum of Schistosoma mansoni, Int. J. Parasitol. 36 (2006) 1e8. [3] A.C. Panda, I. Grammatikakis, K.M. Kim, S. De, J.L. Martindale, R. Munk, et al., Identification of senescence-associated circular RNAs (SAC-RNAs)
reveals senescence suppressor CircPVT1, Nucleic Acids Res. 45 (2017) 4021e4035. [4] Q. Zheng, C. Bao, W. Guo, S. Li, J. Chen, B. Chen, et al., Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs, Nat. Commun. 7 (2016) 11215.
Please cite this article in press as: Y. Li, S. Huang, Response to “Circular RNA profile identifies circPVT1 as a proliferative factor and prognostic marker in gastric cancer,” Cancer Lett. 2017 Mar 1; 388(2017): 208e219, Cancer Letters (2017), http://dx.doi.org/10.1016/j.canlet.2017.05.008
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CAN13352_proof ■ 1 June 2017 ■ 1/2
Cancer Letters xxx (2017) 1e2
Contents lists available at ScienceDirect
Cancer Letters journal homepage: www.elsevier.com/locate/canlet
Commentaries
Q3
Response to “Circular RNA profile identifies circPVT1 as a proliferative factor and prognostic marker in gastric cancer,” Cancer Lett. 2017 Mar 1; 388(2017): 208e219
Q2
Yan Li a, b, Shenglin Huang a, b, * a b
Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
a r t i c l e i n f o Article history: Received 11 May 2017 Accepted 13 May 2017 Keywords: Gastric cancer Circular RNA Proliferation Prognosis
Dear Editor, We much appreciated for the comment on our manuscript [1]. However, there are some misunderstanding in this comment. Firstly, the authors concluded that circPVT1 played a cancer suppressor role in vivo (from the clinical correlation), while was proved to act an oncogene in vitro (from the functional assays). However, the clinical correlation (biomarker) may have no functional implication. We were also very curious about the contradiction between clinical implication and cellular function of circPVT1 in GC. Indeed, we observed similar results in liver cancer (unpublished data). Secondly, the authors claimed that only one study reported the effect of circPVT1 in the past [2]. But this paper published in 2006 did not mention anything about circPVT1 or circRNA. In fact, a most recent paper published in Nucleic Acids Research and reported that circPVT1, elevated in dividing cells and reduced in senescent cells, sequesters let-7 to enable a proliferative phenotype [3]. This function is consistent with our result in GC cells. Thirdly, although we first characterized the circular RNA profile of GC from three paried GC tissues, the expression of circPVT1 was further validated from about 200 patients (Fig. 3A). We used ROC curves to compare
the prognosis of circPVT1 expression, TNM stage and tumor size, all of which are independent prognostic factors. AUC level is relatively low because this analysis is not for diagnosis. We also analyzed the TCGA clinical data, and found similar or lower AUC level. Fourthly, the author claimed that sequence binding between circular RNA and microRNA is usually seven consecutive base complementation pairing at least. However, there are only several papers (including our recent paper published in Nature communications [4]) reported the association of circRNA and miRNA, and the feature about base complementation pairing between circRNA and miRNA remains to be explored. Also sequence binding between miRNA and mRNA is not always seven consecutive base complementation pairing (8mer,7mer-m8 and 7mer-1A). Finally, we found that silencing of circPVT1 inhibits the proliferation of gastric cancer cells and circPVT1 serves as a miRNA sponge for the miR-125 family. The preliminary function and molecular mechanism of circPVT1 was explored in gastric cancer cells. Thanks for the suggestion to detect the detailed molecule indicators of cell proliferation by western blot and flow cytometry. In addition, PVT1 was primarily localized within the nucleus in AGS and MGC-803 cells, because we analysed the localization of PVT1 in AGS (Fig. 2C), MGC-803 (Supplementary Fig. S3A) and HEK-293T cells (data not shown) and found that more than 50% of PVT1 localized in the nucleus in all these three cells (AGS 50%, MGC-803 61%, and HEK-293T 71%). Conflict of interest The author declares no conflict of interest. References [1] J. Chen, Y. Li, Q. Zheng, C. Bao, J. He, B. Chen, et al., Circular RNA profile identifies circPVT1 as a proliferative factor and prognostic marker in gastric cancer, Cancer Lett. 388 (2017) 208e219.
DOI of original article: http://dx.doi.org/10.1016/j.canlet.2017.05.009. * Corresponding author. Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China. E-mail address: [email protected] (S. Huang). http://dx.doi.org/10.1016/j.canlet.2017.05.008 0304-3835/© 2017 Elsevier B.V. All rights reserved.
Please cite this article in press as: Y. Li, S. Huang, Response to “Circular RNA profile identifies circPVT1 as a proliferative factor and prognostic marker in gastric cancer,” Cancer Lett. 2017 Mar 1; 388(2017): 208e219, Cancer Letters (2017), http://dx.doi.org/10.1016/j.canlet.2017.05.008
55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 Q1 116 117 118 119
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Y. Li, S. Huang / Cancer Letters xxx (2017) 1e2
[2] G.P. Dillon, T. Feltwell, J.P. Skelton, P.D. Ashton, P.S. Coulson, M.A. Quail, et al., Microarray analysis identifies genes preferentially expressed in the lung schistosomulum of Schistosoma mansoni, Int. J. Parasitol. 36 (2006) 1e8. [3] A.C. Panda, I. Grammatikakis, K.M. Kim, S. De, J.L. Martindale, R. Munk, et al., Identification of senescence-associated circular RNAs (SAC-RNAs)
reveals senescence suppressor CircPVT1, Nucleic Acids Res. 45 (2017) 4021e4035. [4] Q. Zheng, C. Bao, W. Guo, S. Li, J. Chen, B. Chen, et al., Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs, Nat. Commun. 7 (2016) 11215.
Please cite this article in press as: Y. Li, S. Huang, Response to “Circular RNA profile identifies circPVT1 as a proliferative factor and prognostic marker in gastric cancer,” Cancer Lett. 2017 Mar 1; 388(2017): 208e219, Cancer Letters (2017), http://dx.doi.org/10.1016/j.canlet.2017.05.008
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