title: piR-55490 inhibits the growth of lung carcinoma by suppressing mTOR signaling.
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.
authors.affiliation: Department of Respiratory Medicine, the First Hospital of Jilin University, Jilin, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Peng
authors.affiliation: Department of Respiratory Medicine, the First Hospital of Jilin University, Jilin, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Respiratory Medicine, the First Hospital of Jilin University, Jilin, China.
authors.forename: Chaoying
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Respiratory Medicine, the First Hospital of Jilin University, Jilin, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Lv
authors.affiliation: Department of Pediatrics, the First Hospital of Jilin University, Jilin, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, the First Hospital of Jilin University, Jilin, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jie
authors.affiliation: Department of Respiratory Medicine, the First Hospital of Jilin University, Jilin, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Respiratory Medicine, the First Hospital of Jilin University, Jilin, China. lisa05@yeah.net.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000072283:A549 Cells; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: Akt/mTOR; Lung cancer; piRNA