Abstract 1121: The long non-coding RNA MALAT1 is an essential gene regulator for lung cancer metastasis in a novel human knockout model .

AbstractActin filament associated protein 1 antisense RNA 1 (named AFAP1-AS1) is a long non-coding RNA and overexpressed in many cancers. This study aimed to identify the role and mechanism of AFAP1-AS1 in lung cancer. The AFAP1-AS1 expression was firstly assessed in 187 paraffin-embedded lung cancer and 36 normal lung epithelial tissues by in situ hybridization. The migration and invasion abilities of AFAP1-AS1 were investigated in lung cancer cells. To uncover the molecular mechanism about AFAP1-AS1 function in lung cancer, we screened proteins that interact with AFAP1-AS1 by RNA pull down and the mass spectrometry analyses. AFAP1-AS1 was highly expressed in lung cancer clinical tissues and its expression was positively correlated with lung cancer patients’ poor prognosis. In vivo experiments confirmed that AFAP1-AS1 could promote lung cancer metastasis. AFAP1-AS1 promoted lung cancer cells migration and invasion through interacting with Smad nuclear interacting protein 1 (named SNIP1), which inhibited ubiquitination and degradation of c-Myc protein. Upregulation of c-Myc molecule in turn promoted the expression of ZEB1, ZEB2, and SNAIL gene, which ultimately enhanced epithelial to mesenchymal transition (EMT) and lung cancer metastasis. Understanding the molecular mechanism by which AFAP1-AS1 promotes lung cancer’s migration and invasion may provide novel therapeutic targets for lung cancer patients’ early diagnosis and therapy.

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Long Non-Coding RNA CRYBG3 Promotes Lung Cancer Metastasis via Activating the eEF1A1/MDM2/MTBP Axis

International Journal of Molecular Sciences ◽

10.3390/ijms22063211 ◽

2021 ◽

Vol 22 (6) ◽

pp. 3211

Author(s):

Anqing Wu ◽

Jiaxin Tang ◽

Ziyang Guo ◽

Yingchu Dai ◽

Jing Nie ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Metastasis ◽

Major Barrier ◽

Lung Cancer Metastasis ◽

Non Coding Rna ◽

Metastatic Lung ◽

Associated Proteins ◽

Underlying Mechanisms ◽

Patient Prognosis

The occurrence of distant tumor metastases is a major barrier in non-small cell lung cancer (NSCLC) therapy, and seriously affects clinical treatment and patient prognosis. Recently, long non-coding RNAs (lncRNAs) have been demonstrated to be crucial regulators of metastasis in lung cancer. The aim of this study was to reveal the underlying mechanisms of a novel lncRNA LNC CRYBG3 in regulating NSCLC metastasis. Experimental results showed that LNC CRYBG3 was upregulated in NSCLC cells compared with normal tissue cells, and its level was involved in these cells’ metastatic ability. Exogenously overexpressed LNC CRYBG3 increased the metastatic ability and the protein expression level of the metastasis-associated proteins Snail and Vimentin in low metastatic lung cancer HCC827 cell line. In addition, LNC CRYBG3 contributed to HCC827 cell metastasis in vivo. Mechanistically, LNC CRYBG3 could directly combine with eEF1A1 and promote it to move into the nucleus to enhance the transcription of MDM2. Overexpressed MDM2 combined with MDM2 binding protein (MTBP) to reduce the binding of MTBP with ACTN4 and consequently increased cell migration mediated by ACTN4. In conclusion, the LNC CRYBG3/eEF1A1/MDM2/MTBP axis is a novel signaling pathway regulating tumor metastasis and may be a potential therapeutic target for NSCLC treatment.

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Abstract A21: MALAT-1 is essential for lung cancer metastasis in a novel human knockout model

Cancer Research ◽

10.1158/1538-7445.nonrna12-a21 ◽

2012 ◽

Vol 72 (2 Supplement) ◽

pp. A21-A21

Author(s):

Tony Gutschner ◽

Moritz Eißmann ◽

Monika Hämmerle ◽

Marion Stentrup ◽

Catherina Hildenbrandt ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Metastasis ◽

Lung Cancer Metastasis ◽

Knockout Model

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New Insights into Long Non-Coding RNA MALAT1 in Cancer and Metastasis

Cancers ◽

10.3390/cancers11020216 ◽

2019 ◽

Vol 11 (2) ◽

pp. 216 ◽

Cited By ~ 59

Author(s):

Yutong Sun ◽

Li Ma

Keyword(s):

Cancer Metastasis ◽

Mammalian Species ◽

Model Systems ◽

Normal Tissues ◽

Lung Cancer Metastasis ◽

Non Coding Rna ◽

Cancer Types ◽

Experimental Model Systems ◽

Long Non Coding Rna

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is one of the most abundant, long non-coding RNAs (lncRNAs) in normal tissues. This lncRNA is highly conserved among mammalian species, and based on in vitro results, has been reported to regulate alternative pre-mRNA splicing and gene expression. However, Malat1 knockout mice develop and grow normally, and do not show alterations in alternative splicing. While MALAT1 was originally described as a prognostic marker of lung cancer metastasis, emerging evidence has linked this lncRNA to other cancers, such as breast cancer, prostate cancer, pancreatic cancer, glioma, and leukemia. The role described for MALAT1 is dependent on the cancer types and the experimental model systems. Notably, different or opposite phenotypes resulting from different strategies for inactivating MALAT1 have been observed, which led to distinct models for MALAT1′s functions and mechanisms of action in cancer and metastasis. In this review, we reflect on different experimental strategies used to study MALAT1′s functions, and discuss the current mechanistic models of this highly abundant and conserved lncRNA.

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Wound Healing after Trauma May Predispose to Lung Cancer Metastasis

American Journal of Respiratory Cell and Molecular Biology ◽

10.1165/rcmb.2010-0187rt ◽

2011 ◽

Vol 44 (5) ◽

pp. 591-596 ◽

Cited By ~ 40

Author(s):

Nicholas D. Walter ◽

Pamela L. Rice ◽

Elizabeth F. Redente ◽

Emily F. Kauvar ◽

Lisa Lemond ◽

...

Keyword(s):

Lung Cancer ◽

Wound Healing ◽

Cancer Metastasis ◽

Lung Cancer Metastasis

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FlowCell-enriched circulating tumor cells as a predictor of lung cancer metastasis

Human Cell ◽

10.1007/s13577-021-00500-8 ◽

2021 ◽

Author(s):

Yan Lu ◽

Yushuang Zheng ◽

Yuhong Wang ◽

Dongmei Gu ◽

Jun Zhang ◽

...

Keyword(s):

Lung Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Cancer Metastasis ◽

Lung Tumor ◽

Early Stage ◽

High Rate ◽

Early Stage Lung Cancer ◽

Lung Cancer Metastasis ◽

Number Of Patients

AbstractLung cancer is the most fetal malignancy due to the high rate of metastasis and recurrence after treatment. A considerable number of patients with early-stage lung cancer relapse due to overlooked distant metastasis. Circulating tumor cells (CTCs) are tumor cells in blood circulation that originated from primary or metastatic sites, and it has been shown that CTCs are critical for metastasis and prognosis in various type of cancers. Here, we employed novel method to capture, isolate and classify CTC with FlowCell system and analyzed the CTCs from a cohort of 302 individuals. Our results illustrated that FlowCell-enriched CTCs effectively differentiated benign and malignant lung tumor and the total CTC counts increased as the tumor developed. More importantly, we showed that CTCs displayed superior sensitivity and specificity to predict lung cancer metastasis in comparison to conventional circulating biomarkers. Taken together, our data suggested CTCs can be used to assist the diagnosis of lung cancer as well as predict lung cancer metastasis. These findings provide an alternative means to screen early-stage metastasis.

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Tumor-Derived Exosomal circFARSA Mediates M2 Macrophage Polarization via the PTEN/PI3K/AKT Pathway to Promote Non-small Cell Lung Cancer Metastasis

Cancer Treatment and Research Communications ◽

10.1016/j.ctarc.2021.100412 ◽

2021 ◽

pp. 100412

Author(s):

Tengfei Chen ◽

Yali Liu ◽

Chang Li ◽

Chun Xu ◽

Cheng Ding ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cancer Metastasis ◽

Macrophage Polarization ◽

Small Cell ◽

Akt Pathway ◽

M2 Macrophage ◽

Small Cell Lung ◽

Lung Cancer Metastasis ◽

M2 Macrophage Polarization

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The role of exosomes in lung cancer metastasis and clinical applications: an updated review

Journal of Translational Medicine ◽

10.1186/s12967-021-02985-1 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Lei Yin ◽

Xiaotian Liu ◽

Xuejun Shao ◽

Tao Feng ◽

Jun Xu ◽

...

Keyword(s):

Lung Cancer ◽

Drug Resistance ◽

Cancer Cell ◽

Cancer Metastasis ◽

Value Assessment ◽

Lung Carcinogenesis ◽

Research Attention ◽

Mesenchymal Transition ◽

Lung Cancer Metastasis

AbstractLung cancer is the leading cause of cancer-associated deaths accounting for 24% of all cancer deaths. As a crucial phase of tumor progression, lung cancer metastasis is linked to over 70% of these mortalities. In recent years, exosomes have received increasing research attention in their role in the induction of carcinogenesis and metastasis in the lung. In this review, recent studies on the contribution of exosomes to lung cancer metastasis are discussed, particularly highlighting the role of lung tumor-derived exosomes in immune system evasion, epithelial-mesenchymal transition, and angiogenesis, and their involvement at both the pre-metastatic and metastatic phases. The clinical application of exosomes as therapeutic drug carriers, their role in antitumor drug resistance, and their utility as predictive biomarkers in diagnosis and prognosis are also presented. The metastatic activity, a complex multistep process of cancer cell invasion, survival in blood vessels, attachment and subsequent colonization of the host's organs, is integrated with exosomal effects. Exosomes act as functional mediating factors in cell–cell communication, influencing various steps of the metastatic cascade. To this end, lung cancer cell-derived exosomes enhance cell proliferation, angiogenesis, and metastasis, regulate drug resistance, and antitumor immune activities during lung carcinogenesis, and are currently being explored as an important component in liquid biopsy assessment for diagnosing lung cancer. These nano-sized extracellular vesicles are also being explored as delivery vehicles for therapeutic molecules owing to their unique properties of biocompatibility, circulatory stability, decreased toxicity, and tumor specificity. The current knowledge of the role of exosomes highlights an array of exosome-dependent pathways and cargoes that are ripe for exploiting therapeutic targets to treat lung cancer metastasis, and for predictive value assessment in diagnosis, prognosis, and anti-tumor drug resistance.

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