scholarly journals ZEB1-induced LINC01559 expedites cell proliferation, migration and EMT process in gastric cancer through recruiting IGF2BP2 to stabilize ZEB1 expression

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Huojian Shen ◽  
Hongyi Zhu ◽  
Yuanwen Chen ◽  
Zhiyong Shen ◽  
Weiqing Qiu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Protein Coding ◽  
Mesenchymal Transition ◽  
Cell Proliferation And Migration ◽  
Novel Target ◽  
And Migration ◽  
Proliferation And Migration

AbstractGastric cancer (GC) is a common type of tumor that is characterized with high metastatic rate. In recent years, increasing studies have indicated that lncRNAs are involved in the regulation on cancer cell proliferation and migration. However, the functional role of long intergenic non-protein coding RNA 1559 (LINC01559) in GC is still unclear. In this study, we applied quantitative real-time polymerase chain reaction (RT-qPCR) and examined that LINC01559 expression was significantly enhanced in GC cells. Functional assays such as EdU, colony formation, JC-1 and transwell assays displayed that silencing LINC01559 inhibited cell proliferation and migration while promoted cell apoptosis in GC. Besides, western blot analysis and immunofluorescence assays examined the expression of factors related to epithelial-mesenchymal transition (EMT) and indicated that EMT process was blocked by LINC01559 knockdown in GC cells. Besides, LINC01559 silencing inhibited tumor growth in vivo. In addition, Chromatin immunoprecipitation (ChIP) assays demonstrated that zinc finger E-box binding homeobox 1 (ZEB1) served as a transcription factor to combine with LINC01559 promoter and activated the expression of LINC01559 in GC cells. In return, LINC01559 recruited insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) to stabilize ZEB1 mRNA to up-regulate ZEB1 in GC cells. In short, the findings in this research might provide a novel target for GC treatment.

scholarly journals Purinergic P2Y2 and P2X4 Receptors Are Involved in the Epithelial-Mesenchymal Transition and Metastatic Potential of Gastric Cancer Derived Cell Lines

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1234
Author(s):  
Mauricio Reyna-Jeldes ◽  
Erwin De la Fuente-Ortega ◽  
Daniela Cerda ◽  
Erandi Velázquez-Miranda ◽  
Katherine Pinto ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Purinergic Signaling ◽  
Mesenchymal Transition ◽  
Cell Proliferation And Migration ◽  
P2x4 Receptors ◽  
And Migration ◽  
Proliferation And Migration

Gastric cancer (GC) is a major health concern worldwide, presenting a complex pathophysiology that has hindered many therapeutic efforts so far. In this context, purinergic signaling emerges as a promising pathway for intervention due to its known role in cancer cell proliferation and migration. In this work, we explored in more detail the role of purinergic signaling in GC with several experimental approaches. First, we measured extracellular ATP concentrations on GC-derived cell lines (AGS, MKN-45, and MKN-74), finding higher levels of extracellular ATP than those obtained for the non-tumoral gastric cell line GES-1. Next, we established the P2Y2 and P2X4 receptors (P2Y2R and P2X4R) expression profile on these cells and evaluated their role on cell proliferation and migration after applying overexpression and knockdown strategies. In general, a P2Y2R overexpression and P2X4R downregulation pattern were observed on GC cell lines, and when these patterns were modified, concomitant changes in cell viability were observed. These modifications on gene expression also modified transepithelial electrical resistance (TEER), showing that higher P2Y2R levels decreased TEER, and high P2X4R expression had the opposite effect, suggesting that P2Y2R and P2X4R activation could promote and suppress epithelial-mesenchymal transition (EMT), respectively. These effects were confirmed after treating AGS cells with UTP, a P2Y2R-agonist that modified the expression patterns towards mesenchymal markers. To further characterize the effects of P2Y2R activation on EMT, we used cDNA microarrays and observed that UTP induced important transcriptional changes on several cell processes like cell proliferation induction, apoptosis inhibition, cell differentiation induction, and cell adhesion reduction. These results suggest that purinergic signaling plays a complex role in GC pathophysiology, and changes in purinergic balance can trigger tumorigenesis in non-tumoral gastric cells.

scholarly journals TASP1 Promotes Proliferation and Migration in Gastric Cancer via EMT and AKT/P-AKT Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Xue-Mei Wan ◽  
Xue-Lei Zhou ◽  
Yong-Jun Du ◽  
Hui Shen ◽  
Zhengxia Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Akt Pathway ◽  
Mesenchymal Transition ◽  
Cell Proliferation And Migration ◽  
Potential Biomarker ◽  
And Migration ◽  
The Relationship ◽  
Proliferation And Migration

Threonine aspartase 1 (TASP1) was reported to function in the development of cancer. However, the regulatory mechanism of TASP1 in gastric cancer (GC) remains unclear. In this study, we determined the expression of TASP1 in tissues of GC patients, GC cells by qRT-PCR, and western blot and assessed the relationship between TASP1 and GC cell proliferation and migration via CCK-8 and transwell assay. It was found that the expression of TASP1 in GC tissues or GC cell lines was significantly higher than that in normal adjacent tissues or normal cells. The proliferation and migration of GC cells were inhibited upon TASP1 knockdown. Mechanism investigation revealed that TASP1 promoted GC cell proliferation and migration through upregulating the p-AKT/AKT expression. TASP1 induced GC cell migration via the epithelial -mesenchymal transition (EMT) pathway. In conclusion, TASP1 promotes GC progression through the EMT and AKT/p-AKT pathway, and it may serve as a new potential biomarker and therapeutic target for GC.

scholarly journals miR-26a/b Inhibit Tumor Growth and Angiogenesis by Targeting the HGF-VEGF Axis in Gastric Carcinoma

2017 ◽  
Vol 42 (4) ◽  
pp. 1670-1683 ◽  
Author(s):  
Yiran Si ◽  
Haiyang Zhang ◽  
Tao Ning ◽  
Ming Bai ◽  
Yi Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Luciferase Assay ◽  
Human Gastric Cancer ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Background/Aims: Abnormal expression of HGF is found in various cancers and correlates with tumor proliferation, metastasis and angiogenesis. However, the regulatory mechanism of the HGF-VEGF axis remains unclear. Methods: The expression characteristic of HGF in human gastric cancer tissues was shown by an immunohistochemistry assay, and the expression levels of target protein were detected by Western blot. The relative levels of miR-26a/b and target mRNA were examined by qRT-PCR. We used bioinformatics tools to search for miRNAs that can potentially target HGF. A luciferase assay was used to confirm direct targeting. Furthermore, the functions of miR-26a/b and HGF were evaluated by cell proliferation and migration assays in vitro and by the mouse xenograft tumor model in vivo. Results: We found that the HGF protein was clearly increased while miR-26a/b were dramatically down-regulated in gastric cancer. miR-26a/b directly bind to the 3’-UTR of HGF mRNA at specific targeting sites. We demonstrated that the repression of the HGF-VEGF pathway by miR-26a/b overexpression suppressed gastric cancer cell proliferation and migration. Furthermore, miR-26a/b also showed an anti-tumor effect in the xenograft mouse model by suppressing tumor growth and angiogenesis. Conclusions: miR-26a/b could suppress tumor tumorigenesis and angiogenesis by targeting the HGF-VEGF axis and could serve as a potential treatment modality for targeted therapy in the clinical treatment of gastric cancer.

scholarly journals Overexpression of carboxypeptidase X M14 family member 2 predicts an unfavorable prognosis and promotes proliferation and migration of osteosarcoma

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Xin Zhao ◽  
Ronghang Li ◽  
Qian Wang ◽  
Minfei Wu ◽  
Yanbing Wang
Keyword(s):  
Cell Proliferation ◽  
Family Member ◽  
Western Blotting ◽  
Epithelial Mesenchymal Transition ◽  
Osteosarcoma Cells ◽  
Osteoblast Cells ◽  
Mesenchymal Transition ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Carboxypeptidase X, M14 family member 2 (CPXM2), has been associated with several human developmental disorders. However, whether CPXM2 is involved in oncogenesis or tumor progression remains unclear. Currently, the clinical relevance and function of CPXM2 in human osteosarcoma were investigated. Materials and methods The expression of CPXM2 in osteosarcoma cell lines and tissues were explored by immunohistochemistry and western blotting assays. A eukaryotic expression plasmid was transfected into fetal osteoblast cells to overexpress CPXM2 and the endogenous CPXM2 in osteosarcoma cells was silenced through an RNA interference (RNAi) method transfection. These transfections were validated via western blotting, and the expression levels of several key molecules involved in the epithelial mesenchymal transition was also determined via western blotting. The expression levels of CPXM2 in a fetal osteoblast cell line with CPXM2 overexpressing and an osteosarcoma CPXM2-knockout cell line was confirmed via reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting and immunofluorescence. The malignant phenotype of osteosarcoma cells was indicated by the cholecystokinin octapeptide, colony formation assay, scratch wound healing assay, and Transwell® migration assay. Results We found that CPXM2 was overexpressed in osteosarcoma and that the overexpression was associated with an unfavorable prognosis and tumor node metastasis staging. The knockdown of CPXM2 in cultured osteosarcoma cells significantly impeded cell proliferation and migration. In addition, the upregulation of CPXM2 in fetal osteoblast cells significantly promoted cell proliferation and migration. Besides, western blotting results revealed that several key molecules involved in the epithelial mesenchymal transition (EMT) were regulated by CPXM2. Conclusion Taken together, these results imply an active role for CPXM2 in promoting tumor aggressiveness via epithelial to mesenchymal transition (EMT) modulation in osteosarcoma.

scholarly journals Cancer Susceptibility Candidate 9 (CASC9) Promotes Colorectal Cancer Carcinogenesis via mTOR-Dependent Autophagy and Epithelial–Mesenchymal Transition Pathways

2021 ◽  
Vol 8 ◽  
Author(s):  
Md Zahirul Islam Khan ◽  
Helen Ka Wai Law
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Susceptibility ◽  
Mesenchymal Transition ◽  
Cell Proliferation And Migration ◽  
Hct 116 ◽  
And Migration ◽  
Proliferation And Migration

BackgroundColorectal cancer (CRC) is the third most common cancer worldwide. Many recent studies have demonstrated that different long non-coding RNAs (lncRNAs) are involved in the initiation, advancement, and metastasis of many cancers including CRC. Cancer susceptibility candidate 9 (CASC9) is an lncRNA that has been reported in many cancers, but its role in CRC is poorly understood. In this study, we aimed to examine the expression of CASC9 in CRC cell lines and to determine the mechanism of action of CASC9 in CRC carcinogenesis.MethodsThe expression of CASC9 in CRC tissues was compared with normal samples from publicly available datasets in The Cancer Genome Atlas (TCGA) and The Encyclopedia of RNA Interactomes (ENCORI). CASC9 expression was further verified in four CRC cell lines (DLD1, HT-29, SW480, and HCT-116) and normal colorectal cell line (CCD-112CoN) by real-time quantitative polymerase chain reaction (RT-qPCR). After gene silencing in HCT-116 and SW480, Cell Counting Kit-8 assay, clonogenic assay, and wound healing assay were performed to evaluate cell proliferation, viability, and migration index of cells. Western blotting was used to explore the key pathways involved.ResultsCASC9 was significantly upregulated as analyzed from both public datasets TCGA and ENCORI where its overexpression was associated with poor survival of CRC patients. Similarly, CASC9 was significantly overexpressed in the CRC cell lines compared with normal cells studied. The silencing of CASC9 in HCT-116 and SW480 attenuated cell proliferation and migration significantly. Furthermore, pathways investigations showed that silencing of CASC9 significantly induced autophagy, promoted AMP-activated protein kinase (AMPK) phosphorylation, inhibited mTOR and AKT signaling pathways, and altered epithelial–mesenchymal transition (EMT) marker protein expression.ConclusionWe demonstrated that silencing of CASC9 contributes to the reduced CRC cell proliferation and migration by regulating autophagy and AKT/mTOR/EMT signaling. Therefore, CASC9 plays an important role in carcinogenesis, and its expression may act as a prognostic biomarker and a potential therapeutic target of CRC management.

scholarly journals Assessing the Regulatory Functions of LncRNA SNHG11 in Gastric Cancer Cell Proliferation and Migration

2021 ◽  
Vol 9 ◽  
Author(s):  
Danyi Zhao ◽  
Huawei Chen ◽  
Bing Wang
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Luciferase Reporter ◽  
Cell Proliferation And Migration ◽  
Gastric Cancer Cell Proliferation ◽  
And Migration ◽  
Migration Capacity ◽  
Regulatory Functions ◽  
Proliferation And Migration

The aim of this study was to assess the regulatory functions of SNHG11 in gastric cancer (GC) cell proliferation and migration. Dual-luciferase reporter assay and bioinformatics prediction [starBase (http://starbase.sysu.edu.cn/) and TargetScan (http://www.targetscan.org)] indicated that SNHG11 functions as a miR-184 sponge that can directly act on CDC25A. Compared with normal healthy gastric tissue and mucosal epithelial cell GES-1, SNHG11 and CDC25A expressions were dramatically increased in GC samples and cell lines, whereas microRNA-184 (miR-184) levels were reduced. SNHG11 silencing led to increased miR-184 and reduced CDC25A, whereas miR-184 downregulation recovered the expression of CDC25A. Additionally, miR-184 upregulation also played a role in regulating CDC25A ablation. Then, SNHG11 was silenced or miR-184 was upregulated in two GC cells (SGC-7901 and MKN-28). SNHG11 silencing and miR-184 upregulation caused a notable decrease in GC cell growth and proliferation and increased the apoptotic level of GC cells. Furthermore, SNHG11 silencing and miR-184 upregulation contributed to a decreased migration capacity of GC cells. Downregulated miR-184 expression in SNHG11 silenced GC cells showed that miR-184 inhibition reversed the effect of SNHG11 silencing on the growth, proliferation, apoptosis, and migration of GC cells. Moreover, in vivo xenograft experiments demonstrated that SNHG11 knockdown can inhibit tumor growth. These observations confirmed that SNHG11 acts as an oncogene, whereas miR-194 served as a tumor suppressor in GC development. SNHG11 may provide a new biomarker for GC diagnosis, treatment, and prognosis.

scholarly journals CircACAP2 promotes cell proliferation and migration in lung adenocarcinoma via LASP1-mediated TGF‐β/Smad3 pathway

2021 ◽  
Author(s):  
Jianyu Xu ◽  
Jianli Ma ◽  
Bixi Guan ◽  
Jian Li ◽  
Yan Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Regulatory Mechanism ◽  
Epithelial Mesenchymal Transition ◽  
Circular Rnas ◽  
Mesenchymal Transition ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Abstract Lung adenocarcinoma (LUAD), a common malignant tumor, has led to a great number of deaths around the world. Circular RNAs (circRNAs) have been certified as essential players in the progression of diverse cancers. CircRNA ACAP2 (hsa_circ_0068568) is an oncogene in several cancers. However, the role of circACAP2 in LUAD remains unknown. This study revealed that the expression of circACAP2 was significantly elevated in LUAD tissues and cell lines, especially in the tissues of LUAD patients at advanced stage. Additionally, circACAP2 enhanced cell proliferation, migration, invasion abilities and epithelial-mesenchymal transition (EMT) process in LUAD. Moreover, miR-342-3p interacted with circACAP2 in LUAD cells. Importantly, we found that miR-342-3p targeted LIM and SH3 protein 1 (LASP1), and circACAP2 positively regulated LASP1 expression by competing for miR-342-3p in LUAD. Further, it was confirmed that circACAP2 promoted the malignant behaviors and stimulated the activation of TGF-β/Smad3 pathway in LUAD by modulating the miR-342-3p/LASP1 axis. To conclude, the molecular regulatory mechanism of circACAP2 in LUAD was under discussion in the current study. The findings revealed that circACAP2 facilitated malignant phenotypes in LUAD via the activation of the TGF‐β/Smad3 pathway.

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