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.

Long non-coding RNA HOTTIP promotes renal cell carcinoma progression through the regulation of the miR-506 pathway

“…Former research regarded miR-506 as a tumor suppressive role in various tumors [20][21][22]. However, its role in RCC has not yet been investigated, at least to the best of our knowledge.…”

Non‐coding RNAs are correlated to TGF‐β receptor type 2 in patients with colorectal cancer

“…Some studies have reported that lncRNAs expression levels contribute to onset and progression of CRC. [50][51][52] Chen et al 53 revealed that LAMTOR5-AS1 is remarkably upregulated in non-small cell lung cancer cell tissues. Moreover, in the study conducted by Zaniani et al, 46 LAMTOR5-AS1 was overexpressed in CRC tissues.…”

LncRNA LAMTOR5‐AS1 sponges miR‐210‐3p and regulates cervical cancer progression

“…13 Previous literature has demonstrated that LAMTOR5-AS1 may interfere with the development of different diseases, such as colorectal cancer, non-small-cell carcinoma, and prostate cancer. [14][15][16] The role of LAMTOR5-AS1 in cervical cancer has not been confirmed at this stage. Given the application of LAMTOR5-AS1 in disease, we speculated that it may play a regulatory role in cervical cancer.…”

“…LAMTOR5‐AS1 is located next to the LAMTOR5 gene and is encoded by three exons on human chromosome 1 (p13.3) 13 . Previous literature has demonstrated that LAMTOR5‐AS1 may interfere with the development of different diseases, such as colorectal cancer, non‐small‐cell carcinoma, and prostate cancer 14–16 …”