Positive feedback loop of lncRNA LINC01296/miR‐598/Twist1 promotes non‐small cell lung cancer tumorigenesis

Abstract

Emerging evidence has illustrated the vital roles of long noncoding RNAs (lncRNAs) in human cancers. However, the role of lncRNAs in non-small cell lung cancer (NSCLC) is still elusive and poorly understood. In the current study, our team conducted extensive experiments to identify the role of long intergenic nonprotein coding (LINC01296) on NSCLC tumorigenesis. The results illustrated that the elevated LINC01296 expression in NSCLC tissue specimens and cell lines were closely correlated with the poor prognosis of patients with NSCLC. Functional studies revealed that LINC01296 knockdown silenced by small interfering RNAs inhibited proliferation, accelerated apoptosis in vitro, and impaired tumor growth in vivo.Mechanical studies showed that INC01296 harbored miR-598, acting as a microRNA "sponge." Besides, miR-598 targeted the 3′-UTR of Twist1. Interestingly, transcription factor Twist1 could bind with the promoter of INC01296 and activate its transcriptional level. In summary, we conclude that INC01296/miR-598/Twist1 constitutes a positive feedback loop to promote the tumorigenesis of NSCLC, providing a novel insight and a valuable therapeutic strategy. K E Y W O R D S feedback loop, long intergenic nonprotein coding RNA 01296 (LINC01296), miR-598, non-small cell lung cancer (NSCLC), Twist1

<p>Hsa_circ_RNA_0011780 Represses the Proliferation and Metastasis of Non-Small Cell Lung Cancer by Decreasing FBXW7 via Targeting miR-544a</p>

“…35 A similar positive feedback loop was found in the LINC01296/miR-598/Twist1 axis in NSCLC. 36 These findings indicate that FBXW7 or an FBXW7-related molecule may mediate the transcription of hsa_circ_11780 by functioning as a transcription factor in NSCLC. Nonetheless, this requires further exploration in future studies.…”

“…An increasing number of reports state that interfering with the transcription of ncRNAs, by binding to their promotor regions, is the main feedback pattern of the downstream functional protein. [34][35][36] Zinc finger E-box binding homeobox 1 (ZEB1), which is downstream of the long noncoding RNA (lncRNA) ZEB1 antisense RNA 1(ZEB1-AS)/miR-409-3p, can activate the lncRNA ZEB1-AS expression by binding to its promoter region. 34 lncRNA CASC11 transcription was accelerated when the transcription factor FOXO3 translocated to the promoter of CASC11.…”

Prognostic value of long non-coding RNA 01296 expression in human solid malignant tumours: a meta-analysis

“…LINC01296 has been reported to be dysregulated in different types of cancers. Moreover, LINC01296 was found to play an important role in multiple cellular processes involved in malignant tumour, such as cell proliferation, invasion and migration, by targeting messenger RNA,26 regulating microRNA27 or competing with the endogenous RNA 18. A study from Yuan et al demonstrated that overexpression of LINC01296 was associated with advanced tumour stages and positive lymph node metastasis in patients with pancreatic cancer.…”

“…Long intergenic non-coding RNA 01296 (LINC01296) is a novel intergenic lncRNA located at chromosome 14q11.2 18. Abnormal expression of LINC01296 has been found in various malignant tumours, including colorectal cancer,19 bladder cancer,20 prostate cancer,21 gastric cancer,22 cholangiocarcinoma,23 breast cancer,24 pancreatic cancer,25 osteosarcoma,26 lung cancer27 and oesophageal carcinoma 28. Some studies showed that overexpression of LINC01296 was associated with the clinicopathological features and poor prognosis in different cancers 21 24.…”

H3K27ac-induced lncRNA PAXIP1-AS1 exhibits oncogenic property in ovarian cancer by targeting miR-6744-5p/PCBP2 axis

“…For example, lncRNA CRNDE shows a high level in tongue squamous cell carcinoma tissues and inhibits miR-384 to facilitate cell proliferation and metastasis [11]. Besides, highlyexpressed LINC01296 is revealed to predict poor prognosis in lung cancer patients and enhances tumor growth via modulating miR-598/Twist1 pathway [12]. Importantly, mounting reports indicated that lncRNAs regulate gene expression to mediate cancer progression through multiple ways, such as histone modi cation, transcriptional and post-transcriptional regulation [13].…”