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Long Noncoding RNA LAMTOR5-AS1 Interference Affects MicroRNA-506-3p/ E2F6-Mediated Behavior of Non-Small Cell Lung Cancer Cells

Guojie Chen*1, Kai Wang*1, Guoshu Li†1, Leidong Wang, Yangyang Xiao§, Bo Chen

* Department of Oncology, The First People’s Hospital of Yancheng, The Fourth Affiliated Hospital of Nantong University, Jiangsu, P. R. China
† Department of Respiratory Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, P. R. China
‡ Department of Pathology, Binzhou Medical University Hospital, Shandong, P. R. China
§ Department of Clinical Laboratory, Binzhou Medical University Hospital, Shandong, P. R. China
¶ Department of Infectious Disease, The First People’s Hospital of Yancheng, The Fourth Affiliated Hospital of Nantong University, Jiangsu, P. R. China

Oncology Research 2020, 28(9), 945-959. https://doi.org/10.3727/096504021X16328213967104

Abstract

Long noncoding RNA LAMTOR5 antisense RNA 1 (LAMTOR5-AS1) has been certified as a risk predictor and diagnostic biomarker of prostate cancer. However, the expression and exact roles of LAMTOR5-AS1 in nonsmall cell lung cancer (NSCLC) remain unclear. Thus, we measured LAMTOR5-AS1 expression in NSCLC and gauged its clinical value. The detailed roles and downstream working mechanism of LAMTOR5-AS1 in NSCLC were comprehensively unraveled. qRT-PCR was applied to measure gene expression. Functionally, utilizing small interfering RNA, LAMTOR5-AS1 was ablated, and the functional alterations were addressed by means of different experiments. The targeting activities between LAMTOR5-AS1 and microRNA-506-3p (miR-506-3p) and between miR-506-3p and E2F transcription factor 6 (E2F6) were confirmed by RNA immunoprecipitation and luciferase reporter assays. LAMTOR5-AS1 overexpression in NSCLC was verified in TCGA datasets and our own cohort and manifested an evident relationship with poor prognosis. Interference with LAMTOR5-AS1 led to repression of the proliferation, cloning, and metastasis abilities of NSCLC cells in vitro. We further confirmed an obvious increase in LAMTOR5-AS1-silenced NSCLC cell apoptosis. Furthermore, the absence of LAMTOR5-AS1 restricted tumor growth in vivo. Mechanistically, LAMTOR5- AS1 sponged miR-506-3p in NSCLC cells. Furthermore, E2F6, a downstream target of miR-506-3p, was under the control of LAMTOR5-AS1, which was realized by decoying miR-506-3p. Rescue experiments showed that miR-506-3p suppression or E2F6 reintroduction was capable of remitting LAMTOR5-AS1 deficiencytriggered anticarcinogenic actions in NSCLC. Our study confirmed the exact roles of LAMTOR5-AS1 for the first time and revealed that LAMTOR5-AS1 knockdown disrupts the malignancy of NSCLC by targeting the miR-506-3p/E2F6 axis. Targeting the LAMTOR5-AS1/miR-506-3p/E2F6 pathway may be instrumental for managing patients with NSCLC.

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Cite This Article

APA Style
Chen, G., Wang, K., Li, G., Wang, L., Xiao, Y. et al. (2020). Long noncoding RNA LAMTOR5-AS1 interference affects microrna-506-3p/ e2f6-mediated behavior of non-small cell lung cancer cells. Oncology Research, 28(9), 945-959. https://doi.org/10.3727/096504021X16328213967104
Vancouver Style
Chen G, Wang K, Li G, Wang L, Xiao Y, Chen B. Long noncoding RNA LAMTOR5-AS1 interference affects microrna-506-3p/ e2f6-mediated behavior of non-small cell lung cancer cells. Oncol Res. 2020;28(9):945-959 https://doi.org/10.3727/096504021X16328213967104
IEEE Style
G. Chen, K. Wang, G. Li, L. Wang, Y. Xiao, and B. Chen "Long Noncoding RNA LAMTOR5-AS1 Interference Affects MicroRNA-506-3p/ E2F6-Mediated Behavior of Non-Small Cell Lung Cancer Cells," Oncol. Res., vol. 28, no. 9, pp. 945-959. 2020. https://doi.org/10.3727/096504021X16328213967104



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