miR-12 Derived from Bone Marrow Mesenchymal Stem Cells Accelerates the Development of Human Papillomavirus by Up-Regulating AN1

2022 ◽  
Vol 12 (5) ◽  
pp. 914-919
Author(s):  
Yilidana Mijiti ◽  
Fang Fang ◽  
Shanhui Liang ◽  
Xiuju Huang ◽  
Yilidana Yilihamu ◽  
...  

The miRNA derived from Bone marrow mesenchymal stem cells (BMSCs) have crucial effects on tumors. The tumor could be affected by the abnormal expression of miRNA in human papillomavirus (HPV). Our study aimed to identify the potential brand-new biomarker in order to reveal the pathogenesis of HPV. miRNA derived from BMSCs was detected and identified. The action of miR-12 on biological behavior of HPV was detected. The level of AN1 protein was detected by Western-blot and IHC method. The relationship between miR-12 and AN1 was assessed by bioinformatics analysis and luciferase assay. The tumor cell biological behaviors were evaluated by manipulating miR12 and AN1 level. The tumor volume derived from BMSCs was diminished significantly compared with normal tissues. The tumor volume was bigger after combined injection with Hela cell and miR-12 compared with single injection. The cell proliferative and invasive ability was strengthened after transfection with miR-12mimics. The cell invasive ability was reduced significantly after transfection of si-miR-12. AN1 was a target gene of miR-12 as confirmed by the analysis on bioinformatics and luciferase activity. The phenotype was reversed after the silent presentation of AN1 was disturbed. In conclusion, miR-12 expression is elevated in HPV cells and affects HPV cells through targeting the AN1 signaling pathway.

2020 ◽  
Vol 167 (6) ◽  
pp. 613-621
Author(s):  
Zhongshu Zhai ◽  
Wanhong Chen ◽  
Qiaosheng Hu ◽  
Xin Wang ◽  
Qing Zhao ◽  
...  

Abstract Diabetic osteoporosis (DOP) is attributed to the aberrant physiological function of bone marrow mesenchymal stem cells (BMSCs) under high glucose (HG) environment. MicroRNAs (miRNAs) are involved in the pathological processes of DOP. We aimed to explore the underlying mechanism of miRNA in DOP. BMSCs were cultured in osteogenic medium with HG to induce osteogenic differentiation, and the interaction between miR-493-5p and ZEB2 was assessed by luciferase assay. Herein, we found miR-493-5p is gradually reduced during osteogenic differentiation in BMSCs. HG treatment inhibits osteogenic differentiation and induces an up-regulation of miR-493-5p leading to reduced level of its downstream target ZEB2. Inhibition of miR-493-5p attenuates HG-induced osteogenic differentiation defects by upregulation of ZEB2. Mechanistically, miR-493-5p/ZEB2 signalling mediates HG-inhibited osteogenic differentiation by inactivation of Wnt/β-catenin signalling. More importantly, knockdown of miR-493-5p therapeutically alleviated the DOP condition in mice. HG prevents BMSCs osteogenic differentiation via up-regulation of miR-493-5p, which results in reduced level of ZEB2 by directly targeting its 3′-untranslated region of mRNA. Thus, miR-493-5p/ZEB2 is a potential therapeutic target and provides novel strategy for the treatment and management of DOP.


2020 ◽  
Author(s):  
Zhi Peng ◽  
Zhenkai Lou ◽  
Zhongjie Li ◽  
Shaobo Li ◽  
Kaishun Yang ◽  
...  

Abstract Background: Osteoporosis is the most common bone metabolic disease. Emerging evidence suggests that exosomes are secreted by diverse cells such as bone marrow mesenchymal stem cells (BMSCs), and play important role in cell-to-cell communication and tissue homeostasis. Recently, the discovery of exosomes has attracted attention in the field of bone remodeling. Methods: The exosomes were extracted from BMSCs and labeled by PKH-67, and then incubated with hFOB1.19 cells to investigate the miR-196a function on the osteoblast differentiation of hFOB1.19. The osteoblast differentiation was detected via alizarin red staining and the expression of osteoblast genes were detected by western blot. The cell apoptosis was detected by flow cytometer. The target relationship of miR-196a and Dickkopf-1 (Dkk1) were verified by luciferase assay and western blot. Results: Here we demonstrated that exosomes extracted from BMSCs (BMSC-exo) significantly promoted hFOB1.19 differentiation to osteoblasts. We found that BMSC-exo were enriched with miR-196a and delivered miR-196a to hFOB1.19 cells to inhibit its target Dkk1, which is a negative regulator of Wnt/β-catenin pathway. Conclusion: BMSC-exo activated Wnt/β-catenin pathway to promote osteogenic differentiation, while BMSC-exo failed to exert the effects when miR-196a was deprived. In conclusion, miR-196a delivered by exosomes from BMSCs plays an essential role in enhancing osteoblastic differentiation by targeting Dkk1 to activate Wnt/β-catenin pathway.


2012 ◽  
Vol 3 (6) ◽  
pp. 47 ◽  
Author(s):  
Serena Redaelli ◽  
Angela Bentivegna ◽  
Dana Foudah ◽  
Mariarosaria Miloso ◽  
Juliana Redondo ◽  
...  

2021 ◽  
Author(s):  
Zewei Lin ◽  
Qingqi Ren ◽  
Xiaofei Ma ◽  
Liu Jikui

Abstract Bone marrow mesenchymal stem cells (BM-MSCs) have been shown to exert a potential therapeutic effect during tumor treatment and it has been proved that exosomes derived from BM-MSCs play crucial roles in the progression of malignant tumors. The current study aims to investigate the effect of BM-MSC-derived exosomal microRNA-424-5p (miR-424-5p) on hepatocellular carcinoma (HCC) progression. The expression of miR-424-5p was compared between HCC and adjacent normal tissues, and its prognosis value was analyzed. Additionally, exosomes were extracted from the BM-MSCs and their identity was verified. Luciferase reporter assay was conducted to identify the putative binding sites between miR-424-5p and the 3’-UTR of forkhead box K1 (FOXK1). The BM-MSC-derived exosomes were co-cultured with HCC cells to assess the effect of the BM-MSC-derived exosomes, miR-424-5p, and FOXK1 on the proliferation, migration, invasion, and in vivo tumorigenesis of the HCC cells. Then, the expression of FOXK1 was also examined in HCC and normal tissues. miR-424-5p was downregulated and FOXK1 was upregulated in HCC tissues and cells. BM-MSC-derived exosomes upregulated miR-424-5p expression to suppress the proliferation, migration, invasion, and in vivo tumorigenesis of HCC cells. Knockdown of FOXK1 also repressed the malignant behavior of the HCC cells, and FOXK1 was verified as the target of miR-424-5p. The role of FOXK1 silencing in HCC cells was reversed by miR-424-5p downregulation. Our results suggested that BM-MSC-derived exosomes upregulated miR-424-5p expression to restrain HCC cell growth and invasion via inhibition of FOXK1 expression and as a result, decelerating HCC development.


2021 ◽  
Vol 11 (8) ◽  
pp. 1618-1623
Author(s):  
Lian Chen ◽  
Zhengwen Ruan

Ischemia/reperfusion injury (IRI) causes myocardial damage. Bone marrow mesenchymal stem cells (BMSCs) exert protection on damaged hearts. We studied the effect of BMSCs with highly expressed miR-145 on repairing damaged heart caused by IRI in rats. SD rats were selected to isolate BMSCs which were assigned into negative control group, BMSCs group or miR-145-BMSCs (transfected with a lentivirus carrying pLVX-miR-145) followed by analysis of cell proliferation and apoptosis, and level of miR-145, Bcl2, Bax and VEGF by qRT-PCR. BMSCs overexpressing miR-145 showed elevated proliferation and decreased apoptotic activity. The cardiac function of miR-145-BMSCs and BMSCs rats was improved significantly, Bcl-2 and VEGF expression was enhanced, and Bax was decreased with more significant improvement in miR-145-BMSCs group. miR-145 overexpression has a regulatory effect on the biological behavior of BMSCs, and upregulates Bcl-2, VEGF and other key factors to repair the heart damage caused by IRI and restore heart function.


2013 ◽  
Author(s):  
Melo Ocarino Natalia de ◽  
Silvia Silva Santos ◽  
Lorena Rocha ◽  
Juneo Freitas ◽  
Reis Amanda Maria Sena ◽  
...  

2014 ◽  
Author(s):  
Reis Amanda Maria Sena ◽  
Freitas Silva Juneo de ◽  
Silvia Silva Santos ◽  
Rogeria Serakides ◽  
Melo Ocarino Natalia de

Sign in / Sign up

Export Citation Format

Share Document