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Lung Cancer: Lung Cancer II |

IncRNA F630028O10Rik Contributes to Suppress Lung Cancer in Mice Through Inhibiting miR-223-3p and VEGF Signaling Pathway FREE TO VIEW

Limei Qin; Yijun Yang; Quan Liu; Wanwan Xu; Siting Zhao; Li Qin; Xiaoping Chen
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Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;149(4_S):A304. doi:10.1016/j.chest.2016.02.317
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SESSION TITLE: Lung Cancer II

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM

PURPOSE: Long non-coding RNAs (lncRNAs) are involved in various pathophysiologic processes. Emerging evidence has suggested the role of lncRNAs in human carcinogenesis. Our previous study has demonstrated that Plasmodium infection provides anti-tumor effects in a murine Lewis lung cancer (LLC) model. Therefore we use the Plasmodium-treated mouse model to investigate the role and functional manner of lncRNAs in lung cancer.

METHODS: Lung cancer animal model was established using C57BL/6 mice injected (s.c) with LLC cells; A rodent malarial parasite Plasmodium Yoelli 17xnl strain (P.y) was inoculated (i.p) simultaneously. After 17 days post inoculations, The P.y-treated tumor tissue and the untreated control tissue were isolated for high throughput sequencing of lncRNA. Dysregulated lncRNAs were validated by quantitative RT-PCR. Functional relevance of lncRNAs was elucidated in LLC cells. The regulatory relationship between miRNA and lncRNA was predicted in silico and further validated by luciferase reporter assay and expression analysis.

RESULTS: lncRNA F630028O10RIK was significantly down-regulated in P.y-treated tumor tissues, knock-down of F630028O10RIK could up-regulate transcript expression level of VEGFa, which represented the tumor suppression role of F630028O10RIK. miR-223-3p encoded by F630028O10Rik was found to express in opposite manner to F630028O10Rik, siRNA interference of F630028O10Rik resulted in increasing expression of miR-223-3p. Importantly, miR-223-3p was predicted to bind with F630028O10Rik, which was further validated by luciferase assay. Knock-down of miR-223-3p suppress VEGFa and VEGFR-2, the two most important genes in VEGF signaling pathway.

CONCLUSIONS: lncRNA F630028O10RIK inhibits VEGF signaling pathway in lung cancer by sponging miR-223-3p, which acts as competing endogenous RNAs (ceRNAs) and tumor suppressor.

CLINICAL IMPLICATIONS: lncRNA F630028O10RIK may be used in gene therapy for lung cancer.

DISCLOSURE: The following authors have nothing to disclose: Limei Qin, Yijun Yang, Quan Liu, Wanwan Xu, Siting Zhao, Li Qin, Xiaoping Chen

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