ICAM-1(Intercellular Adhesion Molecule-1) Gene Transfection Inhibits Lymph Node Metastasis by Human Gastric Cancer Cells

tRNA-derived fragments (tRFs) are a new classification of small non-coding RNAs (sncRNAs) derived from the specific cleavage of precursors and mature tRNAs. Accumulating recent evidence has shown that tRFs are frequently abnormal in several cancers. Nevertheless, the role of tRFs in gastric cancer and its mechanism remain unclear. In this study, we found abnormal expression of tRF-3017A (derived from tRNA-Val-TAC) in gastric cancer tissues and cell lines and confirmed its effect on promoting the invasion and migration of gastric cancer cells through functional experiments in vitro. Analysis of clinicopathologic data showed patients with higher tRF-3017A were associated with significantly higher lymph node metastasis. Mechanistic investigation implies that tRF-3017A regulates the tumor suppressor gene NELL2 through forming the RNA-induced silencing complex (RISC) with Argonaute (AGO) proteins. In this study, we found that higher tRF-3017A were associated with significantly higher lymph node metastasis in gastric cancer patients and the tRF-3017A may play a role in promoting the migration and invasion of gastric cancer cells by silencing tumor suppressor NELL2.

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Lymph node metastasis-derived gastric cancer cells educate bone marrow-derived mesenchymal stem cells via YAP signaling activation by exosomal Wnt5a

Oncogene ◽

10.1038/s41388-021-01722-8 ◽

2021 ◽

Vol 40 (12) ◽

pp. 2296-2308

Author(s):

Mei Wang ◽

Xinxin Zhao ◽

Rong Qiu ◽

Zheng Gong ◽

Feng Huang ◽

...

Keyword(s):

Gastric Cancer ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Metastatic Gastric Cancer ◽

Gastric Cancer Cells ◽

Node Metastasis ◽

Signaling Activation

AbstractLymph node metastasis (LNM), a common metastatic gastric-cancer (GC) route, is closely related to poor prognosis in GC patients. Bone marrow-derived mesenchymal stem cells (BM-MSCs) preferentially engraft at metastatic lesions. Whether BM-MSCs are specifically reprogrammed by LNM-derived GC cells (LNM-GCs) and incorporated into metastatic LN microenvironment to prompt GC malignant progression remains unknown. Herein, we found that LNM-GCs specifically educated BM-MSCs via secretory exosomes. Exosomal Wnt5a was identified as key protein mediating LNM-GCs education of BM-MSCs, which was verified by analysis of serum exosomes collected from GC patients with LNM. Wnt5a-enriched exosomes induced YAP dephosphorylation in BM-MSCs, whereas Wnt5a-deficient exosomes exerted the opposite effect. Inhibition of YAP signaling by verteporfin blocked LNM-GC exosome- and serum exosome-mediated reprogramming in BM-MSCs. Analysis of MSC-like cells obtained from metastatic LN tissues of GC patients (GLN-MSCs) confirmed that BM-MSCs incorporated into metastatic LN microenvironment, and that YAP activation participated in maintaining their tumor-promoting phenotype and function. Collectively, our results show that LNM-GCs specifically educated BM-MSCs via exosomal Wnt5a-elicited activation of YAP signaling. This study provides new insights into the mechanisms of LNM in GC and BM-MSC reprogramming, and will provide potential therapeutic targets and detection indicators for GC patients with LNM.

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miR-21 Is a Promising Novel Biomarker for Lymph Node Metastasis in Patients with Gastric Cancer

Gastroenterology Research and Practice ◽

10.1155/2012/640168 ◽

2012 ◽

Vol 2012 ◽

pp. 1-5 ◽

Cited By ~ 18

Author(s):

Yuejuan Xu ◽

Jue Sun ◽

Jianhua Xu ◽

Qi Li ◽

Yuewu Guo ◽

...

Keyword(s):

Gastric Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Malignant Disease ◽

Close Association ◽

Survival Rates ◽

Expression Level ◽

Human Gastric Cancer ◽

Node Metastasis ◽

Kaplan Meier

Background. Gastric cancer (GC) is an important malignant disease around the world. Abnormalities of microRNAs (miRNAs) have been implicated in carcinogenesis of various cancers. In the present study, we examined miR-21 expression in human gastric cancer with lymph node metastasis and attempted to uncover its relationship with clinicopathologic data, especially with lymph node metastasis.Materials and Methods. The expression levels of miR-21 in the tumor specimens of GC patients were quantified by RT-PCR. The correlation between miR-21 level and multiple clinicopathological factors was then examined by Mann-Whitney test, Kaplan-Meier survival analysis, and operating characteristic (ROC) analysis.Results. The expression level of miR-21 was higher in GC patients with lymph node metastasis than in those without lymph node metastasis (P<0.05). Expression level of miR-21 was significantly correlated with histologic type, T stage, lymph node metastasis and pTNM stage. The overall survival rates in GC patients with low upregulated miR-21 expression were significantly higher than those with high upregulated miR-21 (P<0.05).Conclusion. A close association is implicated between the elevated miR-21and lymph node metastasis, which could potentially be exploited as a practical biomarker for lymph node metastasis in patients with GC.

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