LIMD1‐AS1 suppressed non‐small cell lung cancer progression through stabilizing LIMD1 mRNA via hnRNP U

Pan, Jianyuan; Tang, Yongqin; Liu, Shumei; Li, Lily; Yu, Bo; Lu, Yuanyuan; Wang, Yu

doi:10.1002/cam4.2898

Cited by 19 publications

(15 citation statements)

References 29 publications

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“…In general, NAT lncRNAs are able to regulate expression of their sense protein-coding partner genes in cis (so called cis -NATs) ( 57 – 62 ). In line with our findings, LIMD1-AS1 was recently shown to stabilize LIMD1 mRNA in lung cancer ( 41 ). Apart from these epigenetic mechanisms, it is worthy of further investigation of potential transcriptional regulation mediated by other transcription factors, which may be lung cancer specific.…”

Section: Discussionsupporting

confidence: 92%

“…LIMD1-AS1 perfectly correlates with LIMD1 not only in lung cancer, but also in all other types of cancers in the TCGA dataset (Figure 5C). In support of this observation, LIMD1-AS1 was recently shown to stabilize LIMD1 mRNA in a hnRNP-Umediated manner in lung cancer (41). RBSN belongs to the FYVE zinc finger family, members of which bind to the membrane lipid phosphatidylinositol-3-phosphate (PtdIns(3)P) with high specificity.…”

Section: Limd1 Differential Expression and Correlation Patterns In Nsclcmentioning

confidence: 80%

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Algorithm-Based Meta-Analysis Reveals the Mechanistic Interaction of the Tumor Suppressor LIMD1 With Non-Small-Cell Lung Carcinoma

et al. 2021

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Non-small-cell lung carcinoma (NSCLC) is the major type of lung cancer, which is among the leading causes of cancer-related deaths worldwide. LIMD1 was previously identified as a tumor suppressor in lung cancer, but their detailed interaction in this setting remains unclear. In this study, we have carried out multiple genome-wide bioinformatic analyses for a comprehensive understanding of LIMD1 in NSCLC, using various online algorithm platforms that have been built for mega databases derived from both clinical and cell line samples. Our results indicate that LIMD1 expression level is significantly downregulated at both mRNA and protein levels in both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), with a considerable contribution from its promoter methylation rather than its gene mutations. The Limd1 gene undergoes mutation only at a low rate in NSCLC (0.712%). We have further identified LIMD1-associated molecular signatures in NSCLC, including its natural antisense long non-coding RNA LIMD1-AS1 and a pool of membrane trafficking regulators. We have also identified a subgroup of tumor-infiltrating lymphocytes, especially neutrophils, whose tumor infiltration levels significantly correlate with LIMD1 level in both LUAD and LUSC. However, a significant correlation of LIMD1 with a subset of immune regulatory molecules, such as IL6R and TAP1, was only found in LUAD. Regarding the clinical outcomes, LIMD1 expression level only significantly correlates with the survival of LUAD (p<0.01) but not with that of LUSC (p>0.1) patients. These findings indicate that LIMD1 plays a survival role in LUAD patients at least by acting as an immune regulatory protein. To further understand the mechanisms underlying the tumor-suppressing function of LIMD1 in NSCLC, we show that LIMD1 downregulation remarkably correlates with the deregulation of multiple pathways that play decisive roles in the oncogenesis of NSCLC, especially those mediated by EGFR, KRAS, PIK3CA, Keap1, and p63, in both LUAD and LUSC, and those mediated by p53 and CDKN2A only in LUAD. This study has disclosed that LIMD1 can serve as a survival prognostic marker for LUAD patients and provides mechanistic insights into the interaction of LIMD1 with NSCLC, which provide valuable information for clinical applications.

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Section: Discussionsupporting

confidence: 92%

Section: Limd1 Differential Expression and Correlation Patterns In Nsclcmentioning

confidence: 80%

Algorithm-Based Meta-Analysis Reveals the Mechanistic Interaction of the Tumor Suppressor LIMD1 With Non-Small-Cell Lung Carcinoma

et al. 2021

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“… 26 LncRNA LIMD1-AS1 acts as an anti-oncogene to suppress NSCLC progression. 27 LncRNAs, HAS2-AS1 and XIST, accelerate resistance to chemotherapy in NSCLC. 28 , 29 In this study, we found that LINC01089 overexpression inhibited the proliferation, migration, and invasion of A549 and SK-MES-1, suggesting that LINC01089 acts as an anti-oncogene to inhibit tumorigenesis and metastasis in NSCLC.…”

Section: Discussionmentioning

confidence: 99%

<p>Long Intergenic Non-Protein Coding RNA 01089 Weakens Tumor Proliferation, Migration, and Invasion by Sponging miR-3187-3p in Non-Small Cell Lung Cancer</p>

Zhang¹,

Cai²,

Cai³

et al. 2020

CMAR

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Background: Long non-coding RNAs (lncRNAs), a class of endogenous non-coding RNAs, play an important role in the development and metastasis of non-small cell lung cancer (NSCLC). However, the function and mechanism of action of long intergenic nonprotein coding RNA 1089 (LINC01089) in NSCLC remains unclear. This study aimed to identify the role of LINC01089 in cell proliferation, migration, and invasion of NSCLC. Methods: Expression of LINC01089 and the relationship between LINC01089 and overall survival (OS) in NSCLC were determined using GEPIA 2.0. Similarly, microRNAs (miRNAs) that showed increased expression in NSCLC and correlated with OS were identified using the online OncomiR cancer database. Target miRNAs of LINC01089 were predicted using starBase. Cell models of LINC01089 and miR-3187-3p overexpression were constructed using transfection. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to analyze the expression of LINC01089 and miR-3187-3p. MTS assay was used to assess cell proliferation. Transwell was used for migration and invasion assays. Results: LINC01089 expression was significantly reduced in NSCLC tissues and cells. Gain-of-function studies further demonstrated that LINC01089 overexpression inhibited proliferation, migration, and invasion of lung cancer cell lines, A549 and SK-MES-1. Based on starBase prediction and subsequent verification, we revealed that miR-3187-3p is a target miRNA of LINC01089. Additionally, miR-3187-3p expression was significantly increased in NSCLC tissues and cells. Overexpression of miR-3187-3p promoted proliferation, migration, and invasion of A549 and SK-MES-1 cells, thereby reversing the effect of LINC01089. Conclusion: LINC01089 attenuates tumor proliferation, migration, and invasion by sponging miR-3187-3p in NSCLC. LINC01089 acts as a tumor suppressor and represents a potential therapeutic target in NSCLC.

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“…LIMD1 is a member of the Zyxin proteins, encoded at chromosome 3p21.3 and widely expressed in human tissues (22,23). A large number of previous studies have suggested that LIMD1 functions as a tumor suppressor (24)(25)(26)(27). In terms of molecular mechanism, LIMD1 could participate in cellular processes and pathways through its scaffold function, meaning that the tumorsuppressive function of LIMD1 is likely to be regulated by different signal cascades (28).…”

Section: Discussionmentioning

confidence: 99%

miR-550a-5p Functions as a Tumor Promoter by Targeting LIMD1 in Lung Adenocarcinoma

Guo

et al. 2020

Front. Oncol.

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Lung adenocarcinoma accounts for half of all lung cancer cases in most countries. Mounting evidence has demonstrated that microRNAs play important roles in cancer progression, and some of them can be identified as potential biomarkers. This study aimed to explore the role of miR-550a-5p, a lung adenocarcinoma-associated mature microRNA screened out from the TCGA database via R-studio and Perl, with abundant expression in samples and with 5-year survival prognosis difference, as well as having not been studied in lung cancer yet. Potential target genes were predicted by the online database. Gene ontology enrichment, pathway enrichment, protein-protein interaction network, and hub genes-microRNA network were constructed by FunRich, STRING database, and Cytoscape. Then, LIMD1, a known tumor suppressor gene reported by multiple articles, was found to have a negative correlation with miR-550a-5p. The expression of miR-550a-5p was up-regulated in tumor samples and tumor-associated cell lines. Its high expression was also correlated with tumor size. Cell line A549 treated with miR-550a-5p overexpression promoted tumor proliferation, while H1299 treated with miR-550a-5p knockdown showed the opposite result. Mechanically, miR-550a-5p negatively regulated LIMD1 by directly binding to its 3 ′-UTR validated by dual luciferase assay. In summary, a new potential prognostic and therapeutic biomarker, miR-550a-5p, has been identified by bioinformatics analysis and experimental validation in vitro and in vivo, which promotes lung adenocarcinoma by silencing a known suppressor oncogene LIMD1.

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LIMD1‐AS1 suppressed non‐small cell lung cancer progression through stabilizing LIMD1 mRNA via hnRNP U

Cited by 19 publications

References 29 publications

Algorithm-Based Meta-Analysis Reveals the Mechanistic Interaction of the Tumor Suppressor LIMD1 With Non-Small-Cell Lung Carcinoma

Algorithm-Based Meta-Analysis Reveals the Mechanistic Interaction of the Tumor Suppressor LIMD1 With Non-Small-Cell Lung Carcinoma

<p>Long Intergenic Non-Protein Coding RNA 01089 Weakens Tumor Proliferation, Migration, and Invasion by Sponging miR-3187-3p in Non-Small Cell Lung Cancer</p>

miR-550a-5p Functions as a Tumor Promoter by Targeting LIMD1 in Lung Adenocarcinoma

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