scholarly journals LncRNA MIAT as a Stemness-Associated Transcript Regulates the Proliferation, Migration and Metastasis of Glioma

2021 ◽  
Author(s):  
Farzane Amirmahani ◽  
Malek Hossein Asadi ◽  
Sadeq Vallian
Keyword(s):  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Migration Ability ◽  
Altered Expression ◽  
Mesenchymal Transition ◽  
Cycle Arrest ◽  
Non Coding Rna ◽  
Tumor Tissues ◽  
Micro Rnas ◽  
Induced Apoptosis

Abstract Purpose: Glioma is the most prevalent category of brain tumors with cancer stem cells. Myocardial infarction-associated transcript (MIAT) is a long non-coding RNA (lncRNA), with altered expression in different diseases and cancers. The purpose of this study was to evaluate the functional role of lncRNA MIAT in glioma.Methods: In this study, lncRNA MIAT expression was evaluated in the TCGA database in common cancers and glioma specimens. The expression of lncRNA MIAT was knocked down by the RNA interference method, and its effects on the characteristics of two glioma cancer cell lines, A172 and U-87MG, were investigated. Results: The findings of the bioinformatics analysis showed an increase in the expression level of lncRNA MIAT in 12 common cancers. The expression of lncRNA MIAT was much greater in glioma tumor tissues compared to other ones. Knocking-down of lncRNA MIAT led to the reduction of proliferation of glioma cancer cells followed by cell cycle arrest at G1 phase. Furthermore, the inhibition of expression of lncRNA MIAT significantly induced apoptosis, senescence and autophagy, but limited the migration ability and Epithelial-Mesenchymal-Transition (EMT) of cancer cells. Moreover, knocking-down of lncRNA MIAT reduced the expression of stemness factors including Oct4, Sox2, and Nanog. This resulted in the upregulation of their downstream miRNAs (micro RNAs), let-7a-5p and miR-29b-3p. Conclusion: Altogether, our findings showed that lncRNA MIAT could control proliferation, migration and metastasis of glioma cells by regulating the Nanog/ Sox2 / MAP1LC3B2/ let-7a-5p / miR-29b-3p axis. These observations proposed that lncRNA MIAT could be considered as a new oncogene in glioma.

scholarly journals Oxidized Phospholipids in Tumor Microenvironment Stimulate Tumor Metastasis via Regulation of Autophagy

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 558
Author(s):  
Jin Kyung Seok ◽  
Eun-Hee Hong ◽  
Gabsik Yang ◽  
Hye Eun Lee ◽  
Sin-Eun Kim ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Autophagic Flux ◽  
Oxidized Phospholipids ◽  
Mcf7 Cells ◽  
Mesenchymal Transition ◽  
Tumor Tissues

Oxidized phospholipids are well known to play physiological and pathological roles in regulating cellular homeostasis and disease progression. However, their role in cancer metastasis has not been entirely understood. In this study, effects of oxidized phosphatidylcholines such as 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) on epithelial-mesenchymal transition (EMT) and autophagy were determined in cancer cells by immunoblotting and confocal analysis. Metastasis was analyzed by a scratch wound assay and a transwell migration/invasion assay. The concentrations of POVPC and 1-palmitoyl-2-glutaroyl-sn-glycero-phosphocholine (PGPC) in tumor tissues obtained from patients were measured by LC-MS/MS analysis. POVPC induced EMT, resulting in increase of migration and invasion of human hepatocellular carcinoma cells (HepG2) and human breast cancer cells (MCF7). POVPC induced autophagic flux through AMPK-mTOR pathway. Pharmacological inhibition or siRNA knockdown of autophagy decreased migration and invasion of POVPC-treated HepG2 and MCF7 cells. POVPC and PGPC levels were greatly increased at stage II of patient-derived intrahepatic cholangiocarcinoma tissues. PGPC levels were higher in malignant breast tumor tissues than in adjacent nontumor tissues. The results show that oxidized phosphatidylcholines increase metastatic potential of cancer cells by promoting EMT, mediated through autophagy. These suggest the positive regulatory role of oxidized phospholipids accumulated in tumor microenvironment in the regulation of tumorigenesis and metastasis.

scholarly journals EMT Participates in the Regulation of Exosomes Secretion and Function in Esophageal Cancer Cells

2021 ◽  
Vol 20 ◽  
pp. 153303382110330
Author(s):  
Chuangui Chen ◽  
Zhao Ma ◽  
Hongjing Jiang
Keyword(s):  
Esophageal Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Promoting Effect ◽  
Migration Ability ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration ◽  
And Function ◽  
Esophageal Cancer Cells

Epithelial-mesenchymal transition (EMT) is a key step in tumor invasion and distant metastasis. Abundant evidence has documented that exosomes can mediate EMT of tumor cells and endow them with the ability of invasion and migration. However, there are few studies focusing on whether EMT can reverse the secretion of exosomes. In this study, 2 esophageal cancer cells (FLO-1 and SK-GT-4) were selected to compare the migration ability and EMT activation, and to further analyze the secretion ability of exosomes of the 2 cell lines. According to the results, inhibited activation of EMT in FLO-1 cells with relatively high migration ability could effectively reduce the secretion of exosomes. Besides, in SK-GT-4 cells, EMT activation induced by TGF-β could promote the secretion of exosomes. FLO-1 cell derived exosomes exhibited a paracrine effect of promoting the migration of SK-GT-4 cells, and the use of EMT inhibitors could weaken this ability. Furthermore, inhibition of EMT could change the relative content of some miRNAs in exosomes, with a particularly significant downregulation in the expression of miR-196-5p, miR-21-5p and miR-194-5p. Significantly, artificial transfection of the 3 miRNAs into exosomes by electroporation resulted in the recovery of migration-promoting effect of exosomes. Subsequent experiments further revealed that the effect of EMT on these miRNAs could be explained by the intracellular transcription level or the specific sorting mechanism of exosomes. To sum up, our study undoubtedly reveals that EMT has a regulatory effect on exosomes in the quantity and contents in esophageal cancer cells. Significantly, findings in our study provide experimental evidence for the interaction of EMT with the secretion and sorting pathway of exosomes, and also give a new direction for the further study of tumor metastasis.

scholarly journals ALKBH5 Inhibits Pancreatic Cancer Motility by Decreasing Long Non-Coding RNA KCNK15-AS1 Methylation

2018 ◽  
Vol 48 (2) ◽  
pp. 838-846 ◽  
Author(s):  
Yuan He ◽  
Hao Hu ◽  
Yandong Wang ◽  
Hao Yuan ◽  
Zipeng Lu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
The Body ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Cancer Pathogenesis ◽  
Non Coding Rna ◽  
Cancer Tissues ◽  
Long Non Coding Rna

Background/Aims: Mounting evidence suggests that epitranscriptional modifications regulate multiple cellular processes. N6-Methyladenosine (m6A), the most abundant reversible methylation of mRNA, has critical roles in cancer pathogenesis. However, the mechanisms and functions of long non-coding RNA (lncRNA) methylation remain unclear. Pancreatic cancer resulted in 411,600 deaths globally in 2015. By the time of pancreatic cancer diagnosis, metastasis has often occurred in other parts of the body. The present study sought to investigate lncRNA m6A modification and its roles in pancreatic cancer. Methods: Differential expression between cancer cells and matched normal cells was evaluated to identify candidate lncRNAs. The lncRNA KCNK15-AS1 was detected in cancer tissues and various pancreatic cells using RT-qPCR. KCNK15-AS1 was transfected into cells to explore its role in migration and invasion. Then, m6A RNA immunoprecipitation was performed to detect methylated KCNK15-AS1 in tissues and cells. Epithelial–mesenchymal transition (EMT) markers were used to evaluate KCNK15-AS1-mediated EMT processes. Results: KCNK15-AS1 was downregulated in pancreatic cancer tissues compared with paired adjacent normal tissues. KCNK15-AS1 inhibited migration and invasion in MIA PaCa-2 and BxPC-3 cells. Furthermore, total RNA methylation in cancer cells was significantly enriched relative to that in immortalized human pancreatic duct epithelial (HPDE6-C7) cells. In addition, the m6A eraser ALKBH5 was downregulated in cancer cells, which can demethylate KCNK15-AS1 and regulate KCNK15-AS1-mediated cell motility. Conclusion: Our results have revealed a novel mechanism by which ALKBH5 inhibits pancreatic cancer motility by demethylating lncRNA KCNK15-AS1, identifying a potential therapeutic target for pancreatic cancer.

The effect of hepatic stellate cells on hepatocellular carcinoma progression.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 265-265
Author(s):  
Shuichi Iwahashi ◽  
Mitsuo Shimada ◽  
Yuji Morine ◽  
Satoru Imura ◽  
Tetsuya Ikemoto ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Stellate Cells ◽  
Stem Cell Marker ◽  
Cell Marker ◽  
Migration Ability ◽  
Mesenchymal Transition ◽  
And Migration ◽  
E Cadherin

265 Background: The hepatic stellate cells (HSCs) localize at the space of Disse in the liver and have multiple functions. They are identified as the major contributor to hepatic fibrosis. Some manuscripts mentioned that activated HSCs predicted prognoses of hepatocellular carcinoma. The aim of this study is to investigate the effect of HSCs and the role of IL-6 / Stat3 pathway on HCC progression. Methods: HCC cells (Hep G2 and Huh 7) were co-cultured with HSC (LX2 and Li90). The viability and migration ability of cancer cells were detected. Also, the expression of epithelial–mesenchymal transition marker (E-cadherin), stem cell marker (EpCAM and CD44), TGF-b and p-STAT3 of cancer cells were evaluated. Then the IL-6 neutralization was performed during HCC cells and HSCs co-culture. The viability and migration ability of cancer cells were detected. Also, the expression of epithelial–mesenchymal transition marker (E-cadherin), stem cell marker (EpCAM and CD44) and p-STAT3 of cancer cells were evaluated. Results: Co-culture with hepatic stellate cell increased cancer cell viability and migration ability. The expression of E-cadherin, EpCAM and CD44 of cancer cells also increased after co-culture with HSCs. The IL-6 expression and secretion of HSCs were elevated by cancer cell stimulation. The over-expressed IL-6 activated STAT3 of cancer cell showed as the level of phosphorylated STAT3 increased. Neutralized IL-6 during co-culture significantly decrease the viability and migration ability of cancer cells. Also, the expression of E-cadherin, EpCAM and CD44 of cancer cells decreased. Conclusions: HSCs might promote HCC progression through IL-6 / STAT3 pathway.

scholarly journals Long non-coding RNA SNHG6 promotes glioma tumorigenesis by sponging miR-101-3p

2018 ◽  
Vol 33 (2) ◽  
pp. 148-155 ◽  
Author(s):  
Qiang Meng ◽  
Bao-Ying Yang ◽  
Bei Liu ◽  
Ji-Xue Yang ◽  
Yang Sun
Keyword(s):  
Cell Proliferation ◽  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Primary Brain Tumor ◽  
Normal Brain ◽  
Mesenchymal Transition ◽  
Non Coding Rna ◽  
Tumor Tissues ◽  
Glioma Cell Proliferation ◽  
Long Non Coding Rna

Introduction: Glioma is the most common primary brain tumor. The small nucleolar RNA host gene (SNHG) SNHG6 is a potential oncogene in the development of several types of cancers. Methods: In this study, we investigated the functional role of long non-coding RNA (lncRNA) SNHG6 in the malignancy of glioma in cell lines and transplanted nude mice. Results: We found that the expression of lncRNA SNHG6 was higher in glioma tissues and cells than in normal brain tissues and cells. The expression of lncRNA SNHG6 was positively correlated with the malignancy and poor prognosis of glioma patients. microRNA (miR)-101-3p expression was decreased in glioma tissues and cells and was negatively correlated with the malignancy and poor prognosis of glioma patients. In glioma tissues, the expression of lncRNA SNHG6 was negatively correlated with the expression of miR-101-3p. SNHG6 contained a binding site of miR-101-3p. Knockdown of SNHG6 expression resulted in a significant increase of miR-101-3p expression. miR-101-3p mimic markedly decreased the luciferase activity of SNHG6. Knockdown of SNHG6 inhibited glioma cell proliferation, migration, and epithelial-mesenchymal transition (EMT), and increased apoptosis. miR-101-3p mimic enhanced knockdown of SNHG6-induced inhibition of cell proliferation, migration, and EMT, and an increase of apoptosis. Anti-miR-101-3p reversed the the effects of si-SNHG6 on cell malignancy. Knockdown of SNHG6 remarkably reduced the increase of tumor volumes in xenograft mouse models. In tumor tissues, knockdown of SNHG6 increased the expression of miR-101-3p and reduced EMT biomarker expression. Conclusions: Our study provides novel insights into the functions of lncRNA SNHG6/miR-101-3p axis in the tumorigenesis of glioma.

scholarly journals Clinico-Pathological Importance of miR-146a in Lung Cancer

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 274
Author(s):  
Javaid Ahmad Wani ◽  
Sabhiya Majid ◽  
Andleeb Khan ◽  
Azher Arafah ◽  
Ajaz Ahmad ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Anticancer Agents ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Research Field ◽  
Stem Loop ◽  
Altered Expression ◽  
Mesenchymal Transition ◽  
Actual Mechanism ◽  
Micro Rnas

Lung cancer is a well-known malignant tumor of the respiratory tract, which has caused a significant level of damage to human health in the 21st century. Micro-RNAs (miRNAs) are tiny, non-coding RNA stem-loop structures with a length of roughly 20–25 nucleotides that function as powerful modulators of mRNA and protein products of a gene. miRNAs may modulate many biological processes involving growth, differentiation, proliferation, and cell death and play a key role in the pathogenesis of various types of malignancies. Several accumulating pieces of evidence have proven that miRNA, especially miR-146a, are crucial modulators of innate immune response sequences. A novel and exciting cancer research field has involved miRNA for the detection and suppression of cancer. However, the actual mechanism which is adopted by these miRNA is still unclear. miRNAs have been used as a cancer-associated biomarker in several studies, suggesting their altered expression in various cancers compared to the normal cells. The amount of expression of miRNA can also be used to determine the stage of the disease, aiding in early detection. In breast, pancreatic, and hepatocellular carcinoma, and gastric cancer, cancer cell proliferation and metastasis has been suppressed by miR-146a. Changes in miR-146a expression levels have biomarker importance and possess a high potential as a therapeutic target in lung cancer. It retards epithelial-mesenchymal transition and promotes the therapeutic action of anticancer agents in lung cancer. Studies have also suggested that miR-146a affects gene expression through different signaling pathways viz. TNF-α, NF-κB and MEK-1/2, and JNK-1/2. Further research is required for understanding the molecular mechanisms of miR-146a in lung cancer. The potential role of miR-146a as a diagnostic marker of lung cancer must also be analyzed. This review summarizes the tumor-suppressing, anti-inflammatory, and antichemoresistive nature of miR-146a in lung cancer.

Sign in / Sign up

Export Citation Format

Share Document