Tumor‐derived exosomal lncRNA GAS5 as a biomarker for early‐stage non‐small‐cell lung cancer diagnosis

Li, Chuling; Y, Lv; Shao, Chengchen; Chen, Cen; Zhang, Tianli; Wei, Yuqing; Fan, He; Lv, Tangfeng; Liu, Hongbin; Song, Yong

doi:10.1002/jcp.28678

Cited by 128 publications

(78 citation statements)

References 39 publications

(50 reference statements)

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“…For example, a research has provided a proof that the exosomes derived from endothelial progenitor cells can promote the regeneration and differentiation of osteoclast precursors through lncRNA MALAT1, thereby promoting bone repair [27]. It has been showed that expression of the lncRNA GAS5 in secreted exosomes is elevated and exosomes can dynamically monitor the level of GAS5 [28]. Another article has suggested that lncRNA ATB may exert an enormous function on the regulation of the microenvironment of glioma by exosomes [29].…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Exosomal lncRNA HNF1A-AS1 affects cisplatin resistance in cervical cancer cells through regulating microRNA-34b/TUFT1 axis

et al. 2019

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Background: There is growing evidence of the role of long non-coding RNAs (lncRNAs) in cervical cancer (CC). The objective was to discuss whether exosomal lncRNA HNF1A-AS1 impacted drug resistance in CC via binding to microRNA-34b (miR-34b) and regulating TUFT1 expression. Methods: The expression of HNF1A-AS1 in normal cervical epithelial cells, cisplatin (DDP)-sensitive cell line (HeLa/S) and DDP-resistant cell line (HeLa/DDP) cells were detected. HeLa/S and HeLa/DDP cells were interfered with HNF1A-AS1 to determine IC 50 , proliferation, colony formation and apoptosis of CC cells. The exosomes were isolated and identified. Subcellular localization of HNF1A-AS1, expression of miR-34b and TUFT1 in receptor cells were also verified. The binding site between HNF1A-AS1 and miR-34b, together with miR-34b and TUFT1 were confirmed. Tumorigenic ability of cells in nude mice was also detected. Results: HNF1A-AS1 was upregulated in DDP-resistant cell line HeLa/DDP. Silencing HNF1A-AS1 suppressed CC cell proliferation and promoted its apoptosis. HNF1A-AS1 was found to act as a competing endogenous RNA (ceRNA) of miR-34b to promote the expression of TUFT1. Exosomes shuttled HNF1A-AS1 promoted the proliferation and drug resistance of CC cells and inhibited their apoptosis by upregulating the expression of TUFT1 and downregulating miR-34b. Furthermore, suppressed exosomal HNF1A-AS1 in combination with DDP inhibited tumor growth in nude mice. Conclusion: Our study provides evidence that CC-secreted exosomes carrying HNF1A-AS1 as a ceRNA of miR-34b to promote the expression of TUFT1, thereby promoting the DDP resistance in CC cells.

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Exosomal lncRNA HNF1A-AS1 affects cisplatin resistance in cervical cancer cells through regulating microRNA-34b/TUFT1 axis

et al. 2019

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“…Li et al demonstrated that the expression of noncoding RNA growth arrest-specific transcript 5 (GAS5) in circulating exosomes (Exo-GAS5) could be an ideal non-invasive blood-based tumor marker for the identification of patients with early-stage NSCLC. The expression of Exo-GAS5 was significantly lower in NSCLC patients than in healthy controls (p < 0.001) and higher in early-stage compared with advanced-stage NSCLC patients (p = 0.045) [82]. Recently, Zhang et al demonstrated that the expression of exosomal miR-17-5p was significantly higher in NSCLC patients than in healthy controls (p < 0.001).…”

Section: Exosomesmentioning

confidence: 98%

Liquid Biopsy in Non-Small Cell Lung Cancer: Highlights and Challenges

Rijavec

Coco

Genova

et al. 2019

Cancers

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Non-small cell lung cancer is one leading cause of death worldwide, and patients would greatly benefit from an early diagnosis. Since targeted and immunotherapies have emerged as novel approaches for more tailored treatments, repeated assessments of the tumor biology have become pivotal to drive clinical decisions. Currently, tumor tissue biopsy is the gold standard to investigate potentially actionable biomarkers, but this procedure is invasive and may prove inadequate to represent the whole malignancy. In this regard, liquid biopsy represents a minimally invasive and more comprehensive option for early detection and investigation of this tumor. Today, cell-free DNA is the only approved circulating marker to select patients for a targeted therapy. Conversely, the other tumor-derived markers (i.e., circulating tumor cells, miRNAs, exosomes, and tumor educated platelets) are still at a pre-clinical phase, although they show promising results for their application in screening programs or as prognostic/predictive biomarkers. The main challenges for their clinical translation are the lack of reliable cutoffs and, especially for miRNAs, the great variability among the studies. Moreover, no established tool has been approved for circulating tumor cells and exosome isolation. Finally, large prospective clinical trials are mandatory to provide evidence of their clinical utility.

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“…In serum from non-small cell lung cancer (NSCLC) patients, exosomal MALAT-1 (metastasis associated lung adenocarcinoma transcript 1) was higher compared to healthy patients [79] . In contract, serum exosomal GAS5 was down-regulated in NSCLC patients and negatively correlated with tumor stages [80] . Other research group, reported that exosomes containing SOX2-OT (Sox2 overlapping transcript) are enriched in plasma from patients with lung squamous cell carcinoma [81] .…”

Section: Roles Of Exosomal Lncrnasmentioning

confidence: 88%

The role of exosomal long non-coding RNAs in cancer drug resistance

Santos

Dragomir

2019

CDR

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One of the major challenges in oncology is drug resistance, which triggers relapse and shortens patients' survival. In order to promote drug desensitization, cancer cells require the establishment of an ideal tumor microenvironment that accomplishes specific conditions. To achieve this objective, cellular communication is a key factor. Classically, cells were believed to restrictively communicate by ligand-receptor binding, physical cell-to-cell interactions and synapses. Nevertheless, the crosstalk between tumor cells and stroma cells has also been recently reported to be mediated through exosomes, the smallest extracellular vesicles, which transport a plethora of functionally active molecules, such as: proteins, lipids, messenger RNA, DNA, microRNA or long non-coding RNA (lncRNAs). LncRNAs are RNA molecules greater than 200 base pairs that are deregulated in cancer and other diseases. Exosomal lncRNAs are highly stable and can be found in several body fluids, being considered potential biomarkers for tumor liquid biopsy. Exosomal lncRNAs promote angiogenesis, cell proliferation and drug resistance. The role of exosomal lncRNAs in drug resistance affects the main treatment strategies in oncology: chemotherapy, targeted therapy, hormone therapy and immunotherapy. Overall, knowing the molecular mechanisms by which exosomal lncRNA induce pharmacologic resistance could improve further drug development and identify drug resistance biomarkers.

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Tumor‐derived exosomal lncRNA GAS5 as a biomarker for early‐stage non‐small‐cell lung cancer diagnosis

Cited by 128 publications

References 39 publications

RETRACTED ARTICLE: Exosomal lncRNA HNF1A-AS1 affects cisplatin resistance in cervical cancer cells through regulating microRNA-34b/TUFT1 axis

RETRACTED ARTICLE: Exosomal lncRNA HNF1A-AS1 affects cisplatin resistance in cervical cancer cells through regulating microRNA-34b/TUFT1 axis

Liquid Biopsy in Non-Small Cell Lung Cancer: Highlights and Challenges

The role of exosomal long non-coding RNAs in cancer drug resistance

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