scholarly journals LncRNA MONC suppresses the malignant phenotype of Endometrial Cancer Stem Cells and Endometrial Carcinoma Cells by regulating the MiR-636/GLCE axis

2021 ◽  
Author(s):  
Yibing Li ◽  
Jianing Huo ◽  
Junjian He ◽  
xiaoxin Ma
Keyword(s):  
Stem Cells ◽  
Endometrial Cancer ◽  
Cancer Stem Cells ◽  
Endometrial Carcinoma ◽  
Epithelial To Mesenchymal Transition ◽  
Suppressive Effect ◽  
Carcinoma Cells ◽  
Biological Behavior ◽  
Mesenchymal Transition ◽  
Tumor Suppressive Effect

Abstract Background Emerging evidence shows that abnormal expression of long non-coding RNA is involved in the occurrence and development of various tumors. LncRNA MONC is abnormally expressed in head and neck squamous cell carcinoma, lung cancer, colorectal cancer, and acute megakaryocytic leukemia, but the biological function and potential regulatory mechanism of MONC in endometrial cancer stem cells (ECSCs) and endometrial cancer cells (ECCs) have not been studied. Methods We used qRT-PCR to detect the expression of MONC, miR-636 and GLCE in normal human endometrial tissues and endometrial carcinoma tissues. Luciferase assay was used to verify the binding sites between MONC and miR-636 and between miR-636 and GLCE. The double fluorescence in situ hybridization was used to locate MONC and miR-636 in cells. Endometrial cancer stem cells were obtained by Flow cytometry sorting assay. Sphere formation assay, CCK-8 assay, transwell invasion assay, cell cycle analysis and apoptosis assay were used to detect the effects of MONC/miR-636/GLCE axis on the malignant biological behavior of ECSCs and endometrial carcinoma cells (ECCs). The effect of MONC on the epithelial-to-mesenchymal transition (EMT) process was detected using western blot. Finally, we conducted in vivo verification through Tumor xenografts in nude mice. Results In this study, we aimed to explore the tumor suppressive effect and mechanism of MONC in regulating ECSCs and ECCs. We found MONC is low expression in endometrial carcinoma (EC), MONC and miR-636 are relatively co-localized in the cytoplasm. MONC directly inhibits the malignant biological behavior of ECSCs and ECCs by directly inhibiting miR-636. Simultaneously, miR-636 may indirectly reduce the expression of MONC. Down-regulation of miR-636 may promote GLCE expression by targeting the 3'-untranslated region (UTR) of the downstream gene GLCE, thereby inhibiting the progression of ECSCs. MONC combined with miR-636 inhibited tumor epithelial-to-mesenchymal transition (EMT) process. In addition, we verified the tumor suppressive effect of MONC in nude mice, miR-636 can rescue the tumor suppressive effect of overexpressing MONC. Conclusions In conclusion, this study shows that MONC inhibits the malignant phenotypes of ECSCs and ECCs by regulating the miR-636/GLCE axis. The MONC/miR-636/GLCE axis may provide novel treatment avenues for human EC.

scholarly journals LncRNA MONC suppresses the malignant phenotype of Endometrial Cancer Stem Cells and Endometrial Carcinoma Cells by regulating the MiR-636/GLCE axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yibing Li ◽  
Jianing Huo ◽  
Junjian He ◽  
Xiaoxin Ma
Keyword(s):  
Stem Cells ◽  
Endometrial Cancer ◽  
Cancer Stem Cells ◽  
Endometrial Carcinoma ◽  
Nude Mice ◽  
Epithelial To Mesenchymal Transition ◽  
Suppressive Effect ◽  
Biological Behavior ◽  
Mesenchymal Transition ◽  
Tumor Suppressive Effect

Abstract Background Emerging evidence shows that abnormal expression of long non-coding RNA is involved in the occurrence and development of various tumors. LncRNA MONC is abnormally expressed in head and neck squamous cell carcinoma, lung cancer, colorectal cancer, and acute megakaryocytic leukemia, but the biological function and potential regulatory mechanism of MONC in endometrial cancer stem cells (ECSCs) and endometrial cancer cells (ECCs) have not been studied. In this study, we aimed to explore the tumor suppressive effect and mechanism of MONC in regulating ECSCs and ECCs. Methods We used qRT-PCR to detect the expression of MONC, miR-636 and GLCE in normal human endometrial tissues and endometrial carcinoma (EC) tissues. Luciferase assay was used to verify the binding sites between MONC and miR-636 and between miR-636 and GLCE. Double fluorescence in situ hybridization was used to locate MONC and miR-636 in cells. ECSCs were obtained by flow cytometry sorting assay. Sphere formation assay, CCK-8 assay, transwell invasion assay, cell cycle analysis and apoptosis assay were used to detect the effects of MONC/miR-636/GLCE axis on the malignant biological behavior of ECSCs and ECCs. The effect of MONC on the epithelial-to-mesenchymal transition (EMT) process was detected using western blot. Finally, we conducted in vivo verification through Tumor xenografts in BALB/C nude mice. Results In this study, we found MONC is low expression in endometrial carcinoma (EC) and patients in the MONC high-expression group had a better prognosis. MONC and miR-636 are relatively co-localized in the cytoplasm. MONC directly inhibits the malignant biological behavior of ECSCs and ECCs by directly inhibiting miR-636. Simultaneously, miR-636 may indirectly reduce the expression of MONC. Down-regulation of miR-636 may promote GLCE expression by targeting the 3′-untranslated region (UTR) of the downstream gene GLCE, thereby inhibiting the progression of ECSCs. MONC combined with miR-636 inhibited tumor epithelial-to-mesenchymal transition (EMT) process. In addition, we verified the tumor suppressive effect of MONC in nude mice, miR-636 can rescue the tumor suppressive effect of overexpressing MONC. Conclusions In conclusion, this study showed that MONC inhibits the malignant phenotypes of ECSCs and ECCs by regulating the miR-636/GLCE axis. Thus the MONC/miR-636/GLCE axis may provide novel treatment avenues for human EC.

scholarly journals LncRNA MONC Suppresses the Malignant Phenotype of Endometrial Cancer Stem Cells by Regulating the MiR-636/GLCE Axis

2020 ◽  
Author(s):  
Yibing Li ◽  
Jianing Huo ◽  
Junjian He ◽  
Haining Ma ◽  
Xiaoxin Ma
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Endometrial Cancer ◽  
Cancer Stem Cells ◽  
Suppressive Effect ◽  
Luciferase Assay ◽  
Biological Behavior ◽  
Mesenchymal Transition ◽  
Tumor Suppressive Effect

Abstract Background: Emerging evidence shows that abnormal expression of long non-coding RNA is involved in the occurrence and development of various tumors. LncRNA MONC is abnormally expressed in head and neck squamous cell carcinoma (HNSCC), lung cancer, colorectal cancer, and acute megakaryocytic leukemia, but the biological function and potential regulatory mechanism of MONC in endometrial cancer stem cells (ECSCs) and endometrial cancer cells (ECCs) have not been studied. In this study, we aimed to explore the tumor suppressive effect and mechanism of MONC in regulating ECSCs and ECCs. Methods: The expression of genes was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The expression of proteins was detected by Western blot. The interplay of LncRNA-miRNA-mRNA was verified using the luciferase assay. The growth rate of ECSC spheroids was detected by sphere formation assay. Cell proliferation was detected by CCK-8 assay. The cell invasion was detected by transwell invasion assay. Cell cycle was detected by Cell cycle analysis.Cell apoptosis was detected by the Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double-staining assay. Animal study was conducted to evaluate the effect of MONC combined with miR-636 on tumor growth in vivo. Results: Low MONC expression in endometrial carcinoma (EC), which directly inhibits the malignant biological behavior of ECSCs and ECCs by directly inhibiting miR-636. Simultaneously, miR-636 may indirectly reduce the expression of MONC. Down-regulation of miR-636 may promote GLCE expression by targeting the 3'-untranslated region (UTR) of the downstream gene GLCE, thereby inhibiting the progression of ECSCs. MONC combined with miR-636 inhibited the Notch signaling pathway and tumor epithelial-to-mesenchymal transition (EMT) process. In addition, we verified the tumor suppressive effect of MONC in nude mice, miR-636 can rescue the tumor suppressive effect of overexpressing MONC, and this effect is more obvious in ECSC. Conclusion: MONC inhibits the malignant phenotypes of ECSCs and ECCs by regulating the miR-636/GLCE axis. The MONC/miR-636/GLCE axis may provide novel treatment avenues for human EC.

scholarly journals EBV latent membrane proteins promote hybrid epithelial-mesenchymal and extreme mesenchymal states of nasopharyngeal carcinoma cells for tumorigenicity

2021 ◽  
Vol 17 (8) ◽  
pp. e1009873
Author(s):  
Nannan Zhu ◽  
Xiaoting Xu ◽  
Yan Wang ◽  
Musheng Zeng ◽  
Yan Yuan
Keyword(s):  
Stem Cells ◽  
Nasopharyngeal Carcinoma ◽  
Cancer Stem Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Vasculogenic Mimicry ◽  
Metastatic Potential ◽  
Carcinoma Cells ◽  
Tumor Xenograft ◽  
Additional Function ◽  
Mesenchymal Transition

EBV-encoded LMPs are consistently detected in nasopharyngeal carcinoma (NPC). Recent evidence suggests potential roles of LMP1 and LMP2A in Epithelial-to-mesenchymal transition (EMT) process in NPC. EMT engages in the generation and maintenance of cancer stem cells (CSCs) and confers on cancer cells increased tumor-initiating and metastatic potential, and higher resistance to anticancer therapies. However, how LMP1 and LMP2A regulate the EMT process to generate cells with different EMT states and its implications for tumor progression remain unclear. Here we report that LMP1 and LMP2A promote EMT that drives NPC cells from the epithelial-like state (CD104+, CD44low) to epithelial-mesenchymal hybrid (E/M) state (CD104+, CD44high). Furthermore, LMP2A possesses an additional function in stabilizing LMP1 and increasing the level of LMP1 in NPC cells. The elevated LMP1 further forces the EMT to generate extreme-mesenchymal (xM) state cells (CD104-, CD44high). To define the tumorigenic features of cancer stem cells at different states in the EMT spectrum, E, E/M and xM subpopulations were isolated and tested for tumorigenic capability in a tumor xenograft animal model. We found that the cells with E/M phenotypes possess the highest tumor initiating capacity. However, the xM subpopulation exhibits increased vasculogenic mimicry, a hallmark of metastatic cancers. Taken together, coordinated action of LMP1 and LMP2A generates an array of intermediate subpopulations in the EMT spectrum that are responsible for distinct tumorigenic features of NPC such as tumor-initiation, vasculogenesis, and metastasis.

scholarly journals The Role of Autophagy and lncRNAs in the Maintenance of Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1239
Author(s):  
Leila Jahangiri ◽  
Tala Ishola ◽  
Perla Pucci ◽  
Ricky M. Trigg ◽  
Joao Pereira ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Regulatory Networks ◽  
Epithelial To Mesenchymal Transition ◽  
Tumour Microenvironment ◽  
Repair Capacity ◽  
Mesenchymal Transition ◽  
Cellular Processes

Cancer stem cells (CSCs) possess properties such as self-renewal, resistance to apoptotic cues, quiescence, and DNA-damage repair capacity. Moreover, CSCs strongly influence the tumour microenvironment (TME) and may account for cancer progression, recurrence, and relapse. CSCs represent a distinct subpopulation in tumours and the detection, characterisation, and understanding of the regulatory landscape and cellular processes that govern their maintenance may pave the way to improving prognosis, selective targeted therapy, and therapy outcomes. In this review, we have discussed the characteristics of CSCs identified in various cancer types and the role of autophagy and long noncoding RNAs (lncRNAs) in maintaining the homeostasis of CSCs. Further, we have discussed methods to detect CSCs and strategies for treatment and relapse, taking into account the requirement to inhibit CSC growth and survival within the complex backdrop of cellular processes, microenvironmental interactions, and regulatory networks associated with cancer. Finally, we critique the computationally reinforced triangle of factors inclusive of CSC properties, the process of autophagy, and lncRNA and their associated networks with respect to hypoxia, epithelial-to-mesenchymal transition (EMT), and signalling pathways.

scholarly journals Pivotal Role of AKT2 during Dynamic Phenotypic Change of Breast Cancer Stem Cells

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1058 ◽  
Author(s):  
Gener ◽  
Rafael ◽  
Seras-Franzoso ◽  
Perez ◽  
Pindado ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Distant Metastases ◽  
Metastatic Potential ◽  
Phenotypic Change ◽  
Primary Tumors ◽  
Mesenchymal Transition

Therapeutic resistance seen in aggressive forms of breast cancer remains challenging for current treatments. More than half of the patients suffer from a disease relapse, most of them with distant metastases. Cancer maintenance, resistance to therapy, and metastatic disease seem to be sustained by the presence of cancer stem cells (CSC) within a tumor. The difficulty in targeting this subpopulation derives from their dynamic interconversion process, where CSC can differentiate to non-CSC, which in turn de-differentiate into cells with CSC properties. Using fluorescent CSC models driven by the expression of ALDH1A 1(aldehyde dehydrogenase 1A1), we confirmed this dynamic phenotypic change in MDA-MB-231 breast cancer cells and to identify Serine/Threonine Kinase 2 (AKT2) as an important player in the process. To confirm the central role of AKT2, we silenced AKT2 expression via small interfering RNA and using a chemical inhibitor (CCT128930), in both CSC and non-CSC from different cancer cell lines. Our results revealed that AKT2 inhibition effectively prevents non-CSC reversion through mesenchymal to epithelial transition, reducing invasion and colony formation ability of both, non-CSC and CSC. Further, AKT2 inhibition reduced CSC survival in low attachment conditions. Interestingly, in orthotopic tumor mouse models, high expression levels of AKT2 were detected in circulating tumor cells (CTC). These findings suggest AKT2 as a promising target for future anti-cancer therapies at three important levels: (i) Epithelial-to-mesenchymal transition (EMT) reversion and maintenance of CSC subpopulation in primary tumors, (ii) reduction of CTC and the likelihood of metastatic spread, and (iii) prevention of tumor recurrence through inhibition of CSC tumorigenic and metastatic potential.

Sign in / Sign up

Export Citation Format

Share Document