Long non-coding RNA MUC5B-AS1 promotes metastasis through mutually regulating MUC5B expression in lung adenocarcinoma

Yuan, Shuai; Liu, Qingyun; Hu, Zhangxue; Zhou, Zhengyu; Wang, Guilu; Li, Chengying; Xie, Wenting; Ma, Gang; Xiang, Ying; Wu, Na; Wu, Long; Yu, Zhengping; Li, Bai; Li, Yafei

doi:10.1038/s41419-018-0472-6

Cited by 46 publications

(40 citation statements)

References 43 publications

(46 reference statements)

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“…Mounting studies have suggested the significant role of lncRNAs in the development of cancers, including NSCLC [14][15][16]. Herein, we selected LINC00461 for investigation because it has been demonstrated as an oncogene in multiple cancers, such as breast cancer, myeloma, and glioma [17][18][19].…”

Section: Discussionmentioning

confidence: 99%

“…Many lncRNAs have been shown to modulate a wide range of biological behaviors in tumors, such as autophagy, apoptosis, proliferation, invasion, and migration [10][11][12][13]. The effect of lncRNAs on NSCLC has also been uncovered by mounting researches [14][15][16]. Long intergenic non-protein coding RNA 461 (LINC00461) demonstrated oncogenic performance in breast cancer, myeloma, and glioma [17][18][19], promoting cell growth, migration, and invasion, but it is not researched in NSCLC.…”

Section: Introductionmentioning

confidence: 99%

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LINC00461/miR-4478/E2F1 feedback loop promotes non-small cell lung cancer cell proliferation and migration

2020

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Non-small cell lung cancer (NSCLC) is a prevalent subtype of lung cancer, whose mortality is high. Long non-coding RNAs (lncRNAs) have caught rising attentions because of their intricate roles in regulating cancerization and cancer progression. Long intergenic non-protein coding RNA 461 (LINC00461) has recently shown oncogenic potential in several cancers, but the function of LINC00461 in NSCLC remains to be investigated. Our study planned to unveil the regulatory role of LINC00461 in NSCLC. It was validated that LINC00461 was highly expressed in NSCLC tissues and cell lines and exhibited prognostic significance. Furthermore, LINC00461 expression in advanced stage was much higher than in early stage. Loss-of-function experiments suggested that LINC00461 knockdown impaired cell proliferation, migration, and epithelial-to-mesenchymal transition (EMT). Subcellular fractionation revealed the predominant location of LINC00461 in cytoplasm. Mechanistically, LINC00461 up-regulated E2F transcription factor 1 (E2F1) expression through sponging miR-4478. Besides, E2F1 bound to the promoter of LINC00461 to induce its transcription. Finally, rescue experiments verified that LINC00461 aggravated proliferation, migration, and EMT through targeting miR-4478/E2F1 axis. In consequence, the present study illustrated that LINC00461/miR-4478/E2F1 feedback loop promoted NSCLC cell proliferation and migration, providing a new prognostic marker for NSCLC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

LINC00461/miR-4478/E2F1 feedback loop promotes non-small cell lung cancer cell proliferation and migration

2020

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“…Yuan et al demonstrated that MUC5B‐AS1 was up‐regulated and functioned as an oncogene in NSCLC. MUC5B‐AS1 promoted cell migration and invasion by forming a protective RNA‐RNA complex with MUC5B, thereby increasing MUC5B mRNA expression level in NSCLC …”

Section: Main Molecular Mechanism Of Lncrna To Regulate the Metastasimentioning

confidence: 99%

Long non‐coding RNAs: How to regulate the metastasis of non–small‐cell lung cancer

Fang

Wang

Gong

et al. 2020

J Cellular Molecular Medi

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Non–small‐cell lung cancer (NSCLC) has become the most lethal human cancer because of the high rate of metastasis. Hence, clarifying the molecular mechanism underlying NSCLC metastasis is very important to improve the prognosis of patients with NSCLC. Long non‐coding RNAs (LncRNAs) are a class of RNA molecules longer than 200 nucleotides, which can participate in diverse biological processes. About 18% of human LncRNAs were recently found to be associated with tumours. Many studies indicated that aberrant expression of LncRNAs played key roles in the progression and metastasis of NSCLC. According to the function in tumours, LncRNAs can be divided into two classes: oncogenic LncRNAs and tumour‐suppressor LncRNAs. In this review, we summarized the main molecular mechanism of LncRNAs regulating NSCLC metastasis, including three aspects: (a) LncRNAs interact with miRNAs as ceRNAs; (b) LncRNAs bind with target proteins; and (c) LncRNAs participate in the transduction of different signal pathways. Then, LncRNAs can exert their function to regulate the metastasis of NSCLC through influencing the progression of epithelial‐mesenchymal transition (EMT) and the properties of cancer stem cell (CSC). But, it is necessary to do some further research to demonstrate the LncRNAs particular regulatory mechanism of inhibiting the metastasis of NSCLC and explore new drugs targeting LncRNAs.

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“…Long noncoding RNAs (lncRNAs) are a new class of potential biomarkers and therapeutic targets for lung cancer. So far, studies have identi ed various lncRNAs that contribute to cancerous phenotypes such as proliferation, growth suppression, motility, immortality, and angiogenesis in lung cancer [5][6][7][8][9][10]. On the other hand, numerous single nucleotide polymorphisms (SNPs) have been associated with lung cancer risks in the past decade [11].…”

Section: Introductionmentioning

confidence: 99%

SNP rs4142441 and MYC co-modulated long non-coding RNA OSER1-AS1 suppresses non-small cell lung cancer by sequestering RNA-Binding Protein ELAVL1

Xie

Wang

Zhang

et al. 2020

Preprint

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Background: Single nucleotide polymorphisms (SNPs) and long non-coding RNAs (lncRNAs) have been involved in the process of lung cancer. Following clues given by lung cancer risk-associated SNPs, we aimed to find novel functional lncRNAs as candidate targets in non-small cell lung cancer (NSCLC). Methods: Case-control analyses were performed in 626 cases and 736 controls matched up on sex and age. The lncRNA OSER1-AS1 was identified near a lung cancer risk-associated SNP rs4142441. Kaplan–Meier survival analysis was performed to investigate the association between OSER1-AS1 expression and overall survival. The influence of rs4142441 on the expression level of OSER1-AS1 was confirmed using Luciferase assays. Subsequently, the biological function of OSER1-AS1 was assessed in vitro by cell proliferation, migration, and invasion experiments through gain- and loss-of-function approaches, and in vivo by subcutaneous tumor model and tail vein injection lung metastasis model. ChIP and RIP experiments were carried out to investigate the interaction between transcription factors, RNA-binding proteins, and OSER1-AS1.Results: OSER1-AS1 was down-regulated in tumor tissue and its low expression was significantly associated with poor overall survival among non-smokers in NSCLC patients. Gain- and loss-of-function studies revealed that OSER1-AS1 acted as a tumor suppressor by inhibiting lung cancer cell growth, migration and invasion in vitro. Xenograft tumor assays and metastasis mouse model confirmed that OSER1-AS1 suppressed tumor growth and metastasis in vivo. The promoter of OSER1-AS1 was repressed by MYC, and the 3’-end of OSER1-AS1 was competitively targeted by microRNA hsa-miR-17-5p and RNA-binding protein ELAVL1. Conclusion: Our results indicated that OSER1-AS1 exerted tumor-suppressive functions by acting as an ELAVL1 decoy to keep it away from its target mRNAs. Our findings characterized OSER1-AS1 as a new tumor suppressive lncRNA in NSCLC, suggesting that OSER1-AS1 may be suitable as a potential biomarker for prognosis, and a potential target for treatment.

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Long non-coding RNA MUC5B-AS1 promotes metastasis through mutually regulating MUC5B expression in lung adenocarcinoma

Cited by 46 publications

References 43 publications

LINC00461/miR-4478/E2F1 feedback loop promotes non-small cell lung cancer cell proliferation and migration

LINC00461/miR-4478/E2F1 feedback loop promotes non-small cell lung cancer cell proliferation and migration

Long non‐coding RNAs: How to regulate the metastasis of non–small‐cell lung cancer

SNP rs4142441 and MYC co-modulated long non-coding RNA OSER1-AS1 suppresses non-small cell lung cancer by sequestering RNA-Binding Protein ELAVL1

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