CircRNA CircRIMS Acts as a MicroRNA Sponge to Promote Gastric Cancer Metastasis

AbstractThe aberrant classical miRNAs are considered to play significant roles in tumor progression. However, it remains unclear for nonclassical miRNAs, a set of Drosha-independent miRNAs in the process of various biology. Here, we reveal that a nonclassical miR-4646-5p plays a pivotal role in gastric cancer (GC) metastasis. MiR-4646-5p, one of Drosha-independent mirtronic miRNA, is aberrant up-regulated in Drosha-low expressed GC and Drosha-knockdown gastric cancer cells. Mirtronic miR-4646-5p is a specific transcription splicing product of intron 3 of the host gene Abhd16a with the aid of SRSF2. The enhanced miR-4646-5p can stabilize HIF1A by targeting PHD3 to positive feedback regulate Abhd16a and miR-4646-5p itself expressions. ABHD16A, as an emerging phosphatidylserine-specific lipase, involves in lipid metabolism leading to lysophosphatidylserines (lyso-PSs) accumulation, which stimulates RhoA and downstream LIMK/cofilin cascade activity through GPR34/Gi subunit, thus causes metastasis of gastric cancer. In addition, miR-4646-5p/PHD3/HIF1A signaling can also up-regulate RhoA expression and synergistically promote gastric cancer cell invasion and metastasis. Our study provides new insights of nonclassical mirtronic miRNA on tumor progress and may serve as a new diagnostic biomarker for gastric cancer. MiR-4646-5p and its host gene Abhd16a mediated abnormal lipid metabolism may be a new target for clinical treatment of gastric cancer.

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Mutations of key driver genes in gastric cancer metastasis risk: a systematic review and meta-analysis

Expert Review of Molecular Diagnostics ◽

10.1080/14737159.2021.1946394 ◽

2021 ◽

pp. 1-10

Author(s):

Jin Wang ◽

Xinye Shao ◽

Yang Liu ◽

Ruichuan Shi ◽

Bowen Yang ◽

...

Keyword(s):

Gastric Cancer ◽

Systematic Review ◽

Cancer Metastasis ◽

Meta Analysis ◽

Driver Genes ◽

Key Driver

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Long Noncoding RNA Lnc-TLN2-4:1 Suppresses Gastric Cancer Metastasis and Is Associated with Patient Survival

Journal of Oncology ◽

10.1155/2020/8681361 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Yuyun Wu ◽

Ningbo Hao ◽

Suming Wang ◽

Xin Yang ◽

Yufeng Xiao ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Noncoding Rna ◽

Tumor Metastasis ◽

Cancer Metastasis ◽

Survival Rates ◽

Migration And Invasion ◽

Poor Overall Survival ◽

Low Expression ◽

Overall Survival Rates

Gastric cancer (GC) is one of the most common malignancies worldwide, and the tumor metastasis leads to poor outcomes of GC patients. Long noncoding RNAs (lncRNAs) have emerged as new regulatory molecules that play a crucial role in tumor metastasis. However, the biological function and underlying mechanism of numerous lncRNAs in GC metastasis remain largely unclear. Here, we report a novel lncRNA, lnc-TLN2-4:1, whose expression is decreased in GC tissue versus matched normal tissue, and its low expression is involved in the lymph node and distant metastases of GC, as well as poor overall survival rates of GC patients. We further found that lnc-TLN2-4:1 inhibits the ability of GC cells to migrate and invade but does not influence GC cell proliferation and confirmed that lnc-TLN2-4:1 is mainly located in the cytoplasm of GC cells. We then found that lnc-TLN2-4:1 increases the mRNA and protein expression of TLN2 in GC cells and there is a positive correlation between the expression of lnc-TLN2-4:1 and TLN2 mRNA in GC tissue. Collectively, we identified a novel lncRNA, lnc-TLN2-4:1, in GC, where lnc-TLN2-4:1 represses cell migration and invasion. The low expression of lnc-TLN2-4:1 is associated with poor overall survival rates of GC patients. These suggest that lnc-TLN2-4:1 may be a tumor suppressor during GC metastasis.

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Development of a Novel Orthotopic Gastric Cancer Mouse Model

Biological Procedures Online ◽

10.1186/s12575-020-00137-1 ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Wonyoung Kang ◽

Leigh Maher ◽

Michael Michaud ◽

Seong-Woo Bae ◽

Seongyeong Kim ◽

...

Keyword(s):

Gastric Cancer ◽

Mouse Models ◽

Cancer Metastasis ◽

Soft Tissues ◽

Tumor Formation ◽

Cancer Model ◽

Orthotopic Model ◽

Cancer Models ◽

Organotropic Metastasis ◽

Nsg Mouse

Abstract Background Gastric cancer metastasis is a highly fatal disease with a five-year survival rate of less than 5%. One major obstacle in studying gastric cancer metastasis is the lack of faithful models available. The cancer xenograft mouse models are widely used to elucidate the mechanisms of cancer development and progression. Current procedures for creating cancer xenografts include both heterotopic (i.e., subcutaneous) and orthotopic transplantation methods. Compared to the heterotopic model, the orthotopic model has been shown to be the more clinically relevant design as it enables the development of cancer metastasis. Although there are several methods in use to develop the orthotopic gastric cancer model, there is not a model which uses various types of tumor materials, such as soft tissues, semi-liquid tissues, or culture derivatives, due to the technical challenges. Thus, developing the applicable orthotopic model which can utilize various tumor materials is essential. Results To overcome the known limitations of the current orthotopic gastric cancer models, such as exposure of tumor fragments to the neighboring organs or only using firm tissues for the orthotopic implantation, we have developed a new method allowing for the complete insertion of soft tissue fragments or homogeneously minced tissues into the stomach submucosa layer of the immunodeficient NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mouse. With this completely-closed transplantation method, tumors with various types of tissue may be used to establish orthotopic gastric cancer models without the risks of exposure to nearby organs or cell leakage. This surgical procedure was highly reproducible in generating forty-eight mouse models with a surgery success rate of 96% and tumor formation of 93%. Among four orthotopic patient-derived xenograft (PDX) models that we generated in this study, we verified that the occurrence of organotropic metastasis in either the liver or peritoneal cavity was the same as that of the donor patients. Conclusion Here we describe a new protocol, step by step, for the establishment of orthotopic xenograft of gastric cancer. This novel technique will be able to increase the use of orthotopic models in broader applications for not only gastric cancer research but also any research related to the stomach microenvironment.

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A review on the role of Tau and Stathmin in gastric cancer metastasis

European Journal of Pharmacology ◽

10.1016/j.ejphar.2021.174312 ◽

2021 ◽

pp. 174312

Author(s):

Bahareh Zarin ◽

Azadeh Eshraghi ◽

Farzaneh Zarifi ◽

Shaghayegh Haghjooy Javanmard ◽

Ismail Laher ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Metastasis

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ERBB2 kinase domain mutation in a gastric cancer metastasis

Apmis ◽

10.1111/j.1600-0463.2005.apm_284.x ◽

2005 ◽

Vol 113 (10) ◽

pp. 683-687 ◽

Cited By ~ 9

Author(s):

JONG WOO LEE ◽

YOUNG HWA SOUNG ◽

SU YOUNG KIM ◽

WON SANG PARK ◽

SUK WOO NAM ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Metastasis ◽

Kinase Domain ◽

Kinase Domain Mutation

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Knockdown of ARK5 Expression Suppresses Invasion and Metastasis of Gastric Cancer

Cellular Physiology and Biochemistry ◽

10.1159/000478685 ◽

2017 ◽

Vol 42 (3) ◽

pp. 1025-1036 ◽

Cited By ~ 12

Author(s):

Dehu Chen ◽

Guiyuan Liu ◽

Ning Xu ◽

Xiaolan You ◽

Haihua Zhou ◽

...

Keyword(s):

Gastric Cancer ◽

Western Blot ◽

Cancer Metastasis ◽

Epithelial Mesenchymal Transition ◽

Migration And Invasion ◽

Invasion And Metastasis ◽

Ags Cells ◽

Mesenchymal Transition

Background/Aims: Gastric cancer (GC) is a common and lethal malignancy, and AMP-activated protein kinase-related kinase 5 (ARK5) has been discovered to promote cancer metastasis in certain types of cancer. In this study, we explored the role of ARK5 in GC invasion and metastasis. Methods: ARK5 and epithelial-mesenchymal transition (EMT)-related markers were determined by immunohistochemistry and western blot in GC specimens. Other methods including stably transfected against ARK5 into SGC7901 and AGS cells, western blot, migration and invasion assays in vitro and nude mice tumorigenicity in vivo were also employed. Results: The results demonstrated that ARK5 expression was increased and positively correlated with metastasis, EMT-related markers and poor prognosis in patients with GC. Knockdown of ARK5 expression remarkably suppressed GC cells invasion and metastasis via regulating EMT, rather than proliferation in vitro and in vivo. And knockdown of ARK5 expression in GC cells resulted in the down-regulation of the mTOR/p70S6k signals, Slug and SIP1. Conclusion: The elevated ARK5 expression was closely associated with cancer metastasis and patient survival, and it seemed to function in GC cells migration and invasion via EMT alteration, together with the alteration of the mTOR/p70S6k signals, Slug and SIP1, thus providing a potential therapeutic target for GC.

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CDK10 Regulates Gastric Cancer Metastasis By Inhibiting lncRNA-C5ORF42-5 Via Phosphorylation Level of AKT/ERK

10.21203/rs.3.rs-610700/v1 ◽

2021 ◽

Author(s):

Zi-Jian Deng ◽

Dong-Wen Chen ◽

Xi-Jie Chen ◽

Jia-Ming Fang ◽

Liang Xv ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Cell Line ◽

High Throughput ◽

Cancer Metastasis ◽

High Throughput Sequencing ◽

Gastric Cancer Cells ◽

Related Proteins

Abstract Background: Gastric cancer is the fourth most common malignant disease. Both CDK10 and long noncoding RNAs (lncRNAs) have been found to exert biological functions in multiple cancers. However, it is still unclear whether CDK10 represses tumor progression in gastric cancer by reducing potential targeting lncRNAs.Methods: The functions of CDK10 and lncRNA-C5ORF42-5 in proliferation, invasion and migration were assessed by MTS assays, colony formation assays, cell cycle and apoptosis assays, Transwell assays, wound healing assays and animal experiments. We used high-throughput sequencing to confirm the existence of lncRNA-C5ORF42-5 and quantitative real-time PCR was used to evaluate lncRNA expression. Then, with RNA-seq sequencing as well as GO function and KEGG enrichment analysis, we identified the signaling pathways in which lncRNA-C5ORF42-5 was involved in gastric cancer. Finally, western blotting was used to identify the genes regulated by lncRNA-C5ORF42-5.Results: Our results showed that CDK10 is expressed at relatively low levels in gastric cancer cell lines and inhibits the progression of gastric cancer cells both in vitro and in vivo. Next, based on high-throughput sequencing, we identified a novel lncRNA, lncRNA-C5ORF42-5, in the stable CDK10-overexpressing cell line compared with the CDK-knockdown cell line and their controls. Additionally, we confirmed that lncRNA-C5ORF42-5 acts as an oncogene to promote metastasis in gastric cancer in vitro and in vivo. We then ascertained that lncRNA-C5ORF42-5 is a major contributor to the function of CDK10 in gastric cancer metastasis by upregulating lncRNA-C5ORF42-5 to reverse the effects of CDK10 overexpression. Finally, we explored the mechanism by which lncRNA-C5ORF42-5 overexpression affects gastric cancer cells to elucidate whether lncRNA-C5ORF42-5 may increase the activity of the SMAD pathway of BMP signaling and promote the expression of EMT-related proteins, such as E-cadherin. Additionally, overexpression of lncRNA-C5ORF42-5 affected the phosphorylation levels of AKT and ERK.Conclusion: Our findings suggest that CDK10 overexpression represses gastric cancer tumor progression by reducing lncRNA-C5ORF42-5 and hindering activation of the related proteins in metastatic signaling pathways, which provides new insight into developing effective therapeutic strategies in the treatment of metastatic gastric cancer.

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PKM2 Is the Target of a Multi-Herb-Combined Decoction During the Inhibition of Gastric Cancer Progression

Frontiers in Oncology ◽

10.3389/fonc.2021.767116 ◽

2021 ◽

Vol 11 ◽

Author(s):

Qingmin Sun ◽

Mengyun Yuan ◽

Hongxing Wang ◽

Xingxing Zhang ◽

Ruijuan Zhang ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Progression ◽

Cancer Metastasis ◽

Nuclear Translocation ◽

Aerobic Glycolysis ◽

Metabolic Reprogramming ◽

Migration And Invasion ◽

Dependent Manner ◽

Gastric Cancer Cells ◽

Mesenchymal Transition

Gastric cancer is the third leading cause of cancer death worldwide. Traditional Chinese medicine (TCM) is increasingly extensively applied as a complementary therapy for gastric cancer (GC) in China, which shows unique advantages in preventing gastric cancer metastasis. Previous study indicates modified Jian-pi-yang-zheng (mJPYZ) decoction inhibit the progression of gastric cancer by regulating tumor-associated macrophages (TAM). However, it is unclear whether mJPYZ can affect metabolic reprogramming of gastric cancer cells. Here, we showed that mJPYZ effectively attenuated GC cells proliferation, migration and invasion. Meantime, mJPYZ reduced the aerobic glycolysis level of GC cells in vivo and in vitro by regulating the expression and nuclear translocation of PKM2. Overexpression of PKM2 that could reverse the inhibitory effect of mJPYZ, migration and epithelial to mesenchymal transition (EMT). Our results showed PKM2/HIF-1α signaling was the key metabolic regulator of mJPYZ in GC cells. In summary, our present study suggested that abnormal PKM2 is required for maintaining the malignant phenotype of GC cells. The TCM decoction mJPYZ inhibited GC cells growth and EMT by reducing of glycolysis in PKM2 dependent manner. This evidence expanded our understanding of the anti-tumor mechanism of mJPYZ and further indicated mJPYZ a potential anti-tumor agent for GC patients.Chemical Compounds Studied in this ArticleRutin (PubChem CID: 5280805); Lobetyolin (PubChem CID: 53486204); Calycosin-7-glucoside (PubChem CID: 71571502); Formononetin (PubChem CID: 5280378); Calycosin (PubChem CID: 5280448); Ononin (PubChem CID: 442813); P-Coumaric Acid (PubChem CID: 637542).

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