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

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 non-small 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 deficiency-triggered 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.

• Authors: Guojie Chen, Kai Wang, Guoshu Li, Leidong Wang, Yangyang Xiao, Bo Chen
• Journal: Oncology research (Oncol Res) Vol. 28 Issue 9 Pg. 945-959 (Jan 31 2022) ISSN: 1555-3906 [Electronic] United States
• PMID: 34588094 (Publication Type: Journal Article)

Chemical References

• E2F6 Transcription Factor
• E2F6 protein, human
• MIRN506 microRNA, human
• MicroRNAs
• RNA, Long Noncoding

Topics

• Carcinoma, Non-Small-Cell Lung (genetics)
• Cell Line, Tumor
• Cell Proliferation
• E2F6 Transcription Factor
• Gene Expression Regulation, Neoplastic
• Humans
• Lung Neoplasms (genetics)
• Male
• MicroRNAs (genetics)
• RNA, Long Noncoding (genetics)