scholarly journals The tRNA-Derived Fragment-3017A Promotes Metastasis by Inhibiting NELL2 in Human Gastric Cancer

2021 ◽  
Vol 10 ◽  
Author(s):  
Linhao Tong ◽  
Weixu Zhang ◽  
Bicheng Qu ◽  
Fei Zhang ◽  
Zhonghua Wu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Node Metastasis ◽  
Mechanistic Investigation

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.

scholarly journals Decrease in ICAM-1 expression on gastric cancer cells is correlated with lymph node metastasis

1999 ◽  
Vol 2 (4) ◽  
pp. 221-225 ◽  
Author(s):  
Tomofumi Fujihara ◽  
Masakazu Yashiro ◽  
Toru Inoue ◽  
Tetsuji Sawada ◽  
Yasuyuki Kato ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Cancer Cells ◽  
Gastric Cancer Cells ◽  
Node Metastasis

scholarly journals METTL3 promotes the proliferation and mobility of gastric cancer cells

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 25-31 ◽  
Author(s):  
Sen Lin ◽  
Jianing Liu ◽  
Wen Jiang ◽  
Peng Wang ◽  
Chao Sun ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Akt Signaling Pathway ◽  
Gastric Cancer Cells ◽  
Apoptotic Pathway ◽  
Mechanistic Investigation

AbstractMethyltransferase-like 3 (METTL3) was originally known to be responsible for N6-methyladenosine (m6A) modification of mRNA. Recent studies have found that METTL3 plays important roles in a variety of tumors by regulating the translation of oncogenes. However, the functional and regulating mechanisms of METTL3 in human gastric cancer have not yet been understood. Here we knocked down METTL3 in human gastric cancer cell lines, AGS and MKN45, by using shRNA transfection. RT-qPCR assay and western blotting verified the effectiveness of RNA interference on mRNA and protein levels, respectively. Then we found that METTL3 knockdown inhibited cell proliferation, migration and invasion in AGS and MKN45 cells. Moreover, METTL3 knockdown decreased Bcl2 and increased Bax and active Caspase-3 in gastric cancer cells, which suggested the apoptotic pathway was activated. Mechanistic investigation suggested that METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of AKT and expression of down-stream effectors p70S6K and Cyclin D1. In conclusion, our study reveals that down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 may be a potential target for the treatment of human gastric cancer.

scholarly journals The Tumor Suppressor TGFBR3 Blocks Lymph Node Metastasis in Head and Neck Cancer

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1375 ◽  
Author(s):  
Wei-Yu Fang ◽  
Yi-Zih Kuo ◽  
Jang-Yang Chang ◽  
Jenn-Ren Hsiao ◽  
Hung-Ying Kao ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Oral Cancer ◽  
Tumor Suppressor ◽  
Head And Neck ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Node Metastasis ◽  
Oral Cancer Cells

The TGF-β type III receptor (TGFBR3) is an essential constituent of the TGF-β signaling. In this study, we observed a down-regulation of TGFBR3 in oral cancer, a subtype of head and neck cancer (HNC), and patients with low TGFBR3 had poor clinical outcomes. Ectopic expression of TGFBR3 decreased migration and invasion of oral cancer cells and lymph node metastasis of tumors, whereas depletion of TGFBR3 had the opposite effect. In SMAD4-positive OC-2 oral cancer cells, TGFBR3-mediated suppression requires both of its cytoplasmic interacting partners ARRB2 and GIPC1. We demonstrated that TGFBR3 induces the abundance of secreted angiogenin (ANG), a known pro-angiogenic factor, and ANG is essential and sufficient to mediate TGFBR3-dependent inhibition of migration and invasion of oral cancer cells. Notably, in SMAD4-deficient CAL-27 oral cancer cells, only GIPC1 is essential for TGFBR3-induced suppressive activity. Accordingly, HNC patients with low expressions of both TGFBR3 and GIPC1 had the poorest overall survival. In summary, we conclude that TGFBR3 is as a tumor suppressor via SMAD4-dependent and -independent manner in both tumor and stromal cells during oral carcinogenesis. Our study should facilitate the possibility of using TGFBR3-mediated tumor suppression for HNC treatment.

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

Oncogene ◽  
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.

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

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
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.

scholarly journals ZNF139 promotes tumor metastasis by increasing migration and invasion in human gastric cancer cells

Neoplasma ◽  
2014 ◽  
Vol 61 (03) ◽  
pp. 291-298 ◽  
Author(s):  
Y. LI ◽  
B. B. TAN ◽  
Q. ZHAO ◽  
L. Q. FAN ◽  
D. WANG ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Tumor Metastasis ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells

scholarly journals Upregulation of miR-205 induces CHN1 expression, which is associated with the aggressive behaviour of cervical cancer cells and correlated with lymph node metastasis

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jianbing Liu ◽  
Yunfeng Li ◽  
Xihua Chen ◽  
Xiangbo Xu ◽  
Haoqi Zhao ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Lymph Node ◽  
High Risk ◽  
Cell Growth ◽  
Lymph Node Metastasis ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Node Metastasis ◽  
Cervical Cancer Cells ◽  
Human Cervical Cancer

Abstract Background Cervical cancer is the leading cause of cancer-related death in women worldwide. However, the mechanisms mediating the development and progression of cervical cancer are unclear. In this study, we aimed to elucidate the roles of microRNAs and a1-chimaerin (CHN1) protein in cervical cancer progression. Methods The expression of miR-205 and CHN1 protein was investigated by in situ hybridisation and immunohistochemistry. We predicted the target genes of miR-205 using software prediction and dual luciferase assays. The expression of mRNAs and proteins was tested by qRT-PCR and western blotting respectively. The ability of cell growth, migration and invasion was evaluated by CCK-8 and transwell. Cell apoptosis was analysed by flow cytometry analysis. Results We found that miR-205 and CHN1 were highly expressed in human cervical cancer tissue compared with paired normal cervical tissues. The CHN1 gene was shown to be targeted by miR-205 in HeLa cells. Interestingly, transfection with miR-205 mimic upregulated CHN1 mRNA and protein, while miR-205 inhibitor downregulated CHN1 in high-risk and human papilloma virus (HPV)-negative human cervical cancer cells in vitro,. These data suggested that miR-205 positively regulated the expression of CHN1. Furthermore, the miR-205 mimic promoted cell growth, apoptosis, migration, and invasion in high-risk and HPV-negative cervical cancer cells, while the miR-205 inhibitor blocked these biological processes. Knockdown of CHN1 obviously reduced the aggressive cellular behaviours induced by upregulation of miR-205, suggesting that miR-205 positively regulated CHN1 to mediate these cell behaviours during the development of cervical cancer. Furthermore, CHN1 was correlated with lymph node metastasis in clinical specimens. Conclusions Our findings showed that miR-205 positively regulated CHN1 to mediate cell growth, apoptosis, migration, and invasion during cervical cancer development, particularly for high-risk HPV-type cervical cancer. These findings suggested that dysregulation of miR-205 and subsequent abnormalities in CHN1 expression promoted the oncogenic potential of human cervical cancer.

scholarly journals MicroRNA-219-5p Represses the Proliferation, Migration, and Invasion of Gastric Cancer Cells by Targeting the LRH-1/Wnt/β-Catenin Signaling Pathway

2017 ◽  
Vol 25 (4) ◽  
pp. 617-627 ◽  
Author(s):  
Chunsheng Li ◽  
Jingrong Dong ◽  
Zhenqi Han ◽  
Kai Zhang
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Human Cancer ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Cancer Tissues

MicroRNAs (miRNAs) are reportedly involved in gastric cancer development and progression. In particular, miR-219-5p has been reported to be a tumor-associated miRNA in human cancer. However, the role of miR-219-5p in gastric cancer remains unclear. In this study, we investigated for the first time the potential role and underlying mechanism of miR-219-5p in the proliferation, migration, and invasion of human gastric cancer cells. miR-219-5p was found to be markedly decreased in gastric cancer tissues and cell lines compared with adjacent tissues and normal gastric epithelial cells. miR-219-5p mimics or anti-miR-219-5p was transfected into gastric cancer cell lines to overexpress or suppress miR-219-5p expression, respectively. Results showed that miR-219-5p overexpression significantly decreased the proliferation, migration, and invasion of gastric cancer cells. Conversely, miR-219-5p suppression demonstrated a completely opposite effect. Bioinformatics and luciferase reporter assays indicated that miR-219-5p targeted the 3′-untranslated region of the liver receptor homolog-1 (LRH-1), a well-characterized oncogene. Furthermore, miR-219-5p inhibited the mRNA and protein levels of LRH-1. LRH-1 mRNA expression was inversely correlated with miR-219-5p expression in gastric cancer tissues. miR-219-5p overexpression significantly decreased the Wnt/β-catenin signaling pathway in gastric cancer cells. Additionally, LRH-1 restoration can markedly reverse miR-219-5p-mediated tumor suppressive effects. Our study suggests that miR-219-5p regulated the proliferation, migration, and invasion of human gastric cancer cells by suppressing LRH-1. miR-219-5p may be a potential target for gastric cancer therapy.

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