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piR-55490 inhibits the growth of lung carcinoma by suppressing mTOR signaling

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Tumor Biology

Abstract

Lung carcinoma is the most common human cancer with poor prognosis and has an increasing incidence in recent years. However, the related mechanism of lung cancer onset has not been completely explored. Piwi-interacting RNA (piRNA) is a type of noncoding small RNA with established function in germ cells, and interestingly, piRNA has also been shown to be implicated in cancer biology. In this study, piR-55490 was found to be silenced in lung carcinoma specimens and cell lines, compared with normal lung tissues and cells. Intriguingly, the expression level of piR-55490 is negatively associated with patients’ survival. Restoration of piR-55490 can reduce the proliferation rates of lung cancer cells, while piR-55490 suppression led to the gain in the proliferation rates. Animal model study showed that piR-55490 can suppress the growth of lung carcinoma xenograft. Further study revealed that piR-55490 suppressed the activation of Akt/mTOR pathway in lung cancer cells. Surprisingly, piR-55490 was found to bind 3′UTR of mTOR messenger RNA (mRNA) and induce its degradation in a mechanism similar to microRNA (miRNA). The introduction of an mTOR construct resistant to action of piR-55490 was able to abolish the effect of piR-55490 on lung cancer cells. In conclusions, we found that piRNA can contribute to the suppression of cancer cell phenotypes by directly targeting a oncogene mRNA. This finding facilitates our understanding of piRNA’s function and its association with human cancer.

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References

  1. Smith RA, Manassaram-Baptiste D, Brooks D, Doroshenk M, Fedewa S, Saslow D, et al. Cancer screening in the United States, 2015: a review of current American cancer society guidelines and current issues in cancer screening. CA Cancer J Clin. 2015;65(1):30–54. doi:10.3322/caac.21261.

    Article  PubMed  Google Scholar 

  2. Hale BJ, Yang CX, Ross JW. Small RNA regulation of reproductive function. Mol Reprod Dev. 2014;81(2):148–59. doi:10.1002/mrd.22272.

    Article  CAS  PubMed  Google Scholar 

  3. Cheng J, Guo JM, Xiao BX, Miao Y, Jiang Z, Zhou H, et al. piRNA, the new non-coding RNA, is aberrantly expressed in human cancer cells. Clin Chim Acta Int J Clin Chem. 2011;412(17–18):1621–5. doi:10.1016/j.cca.2011.05.015.

    Article  CAS  Google Scholar 

  4. Cui L, Lou Y, Zhang X, Zhou H, Deng H, Song H, et al. Detection of circulating tumor cells in peripheral blood from patients with gastric cancer using piRNAs as markers. Clin Biochem. 2011;44(13):1050–7. doi:10.1016/j.clinbiochem.2011.06.004.

    Article  CAS  PubMed  Google Scholar 

  5. Cheng J, Deng H, Xiao B, Zhou H, Zhou F, Shen Z, et al. piR-823, a novel non-coding small RNA, demonstrates in vitro and in vivo tumor suppressive activity in human gastric cancer cells. Cancer Lett. 2012;315(1):12–7. doi:10.1016/j.canlet.2011.10.004.

    Article  CAS  PubMed  Google Scholar 

  6. Yan H, Wu QL, Sun CY, Ai LS, Deng J, Zhang L, et al. piRNA-823 contributes to tumorigenesis by regulating de novo DNA methylation and angiogenesis in multiple myeloma. Leukemia. 2015;29(1):196–206. doi:10.1038/leu.2014.135.

    Article  CAS  PubMed  Google Scholar 

  7. Huang G, Hu H, Xue X, Shen S, Gao E, Guo G, et al. Altered expression of piRNAs and their relation with clinicopathologic features of breast cancer. Clin Transl Oncol Off Publ Fed Spanish Oncol Soc Nat Cancer Inst Mexico. 2013;15(7):563–8. doi:10.1007/s12094-012-0966-0.

    CAS  Google Scholar 

  8. Law PT, Qin H, Ching AK, Lai KP, Co NN, He M, et al. Deep sequencing of small RNA transcriptome reveals novel non-coding RNAs in hepatocellular carcinoma. J Hepatol. 2013;58(6):1165–73. doi:10.1016/j.jhep.2013.01.032.

    Article  CAS  PubMed  Google Scholar 

  9. Zhang H, Ren Y, Xu H, Pang D, Duan C, Liu C. The expression of stem cell protein Piwil2 and piR-932 in breast cancer. Surg Oncol. 2013;22(4):217–23. doi:10.1016/j.suronc.2013.07.001.

    Article  PubMed  Google Scholar 

  10. Chu H, Hui G, Yuan L, Shi D, Wang Y, Du M, et al. Identification of novel piRNAs in bladder cancer. Cancer Lett. 2015;356(2 Pt B):561–7. doi:10.1016/j.canlet.2014.10.004.

    Article  CAS  PubMed  Google Scholar 

  11. Li Y, Wu X, Gao H, Jin JM, Li AX, Kim YS, et al. PIWI-interacting RNAs are dysregulated in renal cell carcinoma and associated with tumor metastasis and cancer specific survival. Mol Med. 2015. doi:10.2119/molmed.2014.00203.

    Google Scholar 

  12. Siddiqi S, Matushansky I. Piwis and piwi-interacting RNAs in the epigenetics of cancer. J Cell Biochem. 2012;113(2):373–80. doi:10.1002/jcb.23363.

    Article  CAS  PubMed  Google Scholar 

  13. Shan J, Shen J, Liu L, Xia F, Xu C, Duan G, et al. Nanog regulates self-renewal of cancer stem cells through the insulin-like growth factor pathway in human hepatocellular carcinoma. Hepatology. 2012;56(3):1004–14. doi:10.1002/hep.25745.

    Article  CAS  PubMed  Google Scholar 

  14. Yip PY. Phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin (PI3K-Akt-mTOR) signaling pathway in non-small cell lung cancer. Transl Lung Cancer Res. 2015;4(2):165–76. doi:10.3978/j.issn.2218-6751.2015.01.04.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Croce CM, Calin GA. miRNAs, cancer, and stem cell division. Cell. 2005;122(1):6–7. doi:10.1016/j.cell.2005.06.036.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Respiratory Medicine, the First Hospital of Jilin University, Jilin, China

    Liping Peng, Lei Song, Chaoying Liu, Xiaohong Lv, Jing Jie, Dan Zhao & Dan Li

  2. Department of Pediatrics, the First Hospital of Jilin University, Jilin, China

    Xiaoping Li

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  1. Liping Peng
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  2. Lei Song
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  3. Chaoying Liu
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  4. Xiaohong Lv
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  5. Xiaoping Li
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  6. Jing Jie
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  7. Dan Zhao
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  8. Dan Li
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Correspondence to Dan Li.

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Peng, L., Song, L., Liu, C. et al. piR-55490 inhibits the growth of lung carcinoma by suppressing mTOR signaling. Tumor Biol. 37, 2749–2756 (2016). https://doi.org/10.1007/s13277-015-4056-0

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  • DOI: https://doi.org/10.1007/s13277-015-4056-0

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