Fig 5 - available via license: Creative Commons Attribution 4.0 International
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RhoB signaling is involved in the proliferation inhibition of Dex in MG-63 cells. (A) MG-63 cells were cultured in medium containing 0-1000 nM Dex for 0, 2, 4 and 6 days, respectively. (B) The transfected cells were cultured in medium containing 5% dextran-coated charcoal treated fetal calf serum for 24 h, then changed to the same medium supplied with 0-100 nM Dex and cultured for 4 days. The proliferation in monolayer culture was monitored by cell number counting. Data are means ± S.D. of four independent experiments. Symbol * or # represents p<0.05, ** represents p<0.01. https://doi.org/10.1371/journal.pone.0174273.g005
Source publication
Long-term exposure to therapeutic doses of glucocorticoids (GCs) results in bone remodeling, which frequently causes osteoporosis and fracture healing retardation because of the abnormality of osteoblastic proliferation and differentiation. The mechanisms of GCs’ effect on osteoblasts are largely unknown. In this present study, we found that dexame...
Citations
... RhoB is a small (~21 kDa) protein of the Rho GTPase family that includes proteins such as RhoA, RhoC, Rac1, and Cdc42 [23]. RhoB is involved in biological process such as cell proliferation, migration, adhesion, differentiation, and angiogenesis [24][25][26]. To evaluate the role of RhoB in improving ED, we performed cell viability and tube formation assays after downregulating RhoB level with siRNA. ...
Purpose:
To evaluate the therapeutic effect of repeated injections of mesenchymal stem cell (MSC)-derived exosomes on the erectile dysfunction (ED) of bilateral cavernous nerve injury (BCNI) rat model and to identify potential target genes of these injections.
Materials and methods:
MSC-derived exosomes were isolated using an aqueous two-phase system. Rats were randomly assigned into four groups: Normal, BCNI, exosome once, and exosome-repeat groups. After four weeks, we measured the intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio to evaluate erectile function and examined cavernous nerve tissues for histological and molecular analyses. RNA sequencing in penile tissues was used to determine differentially expressed genes and was verified by quantitative polymerase chain reaction. Human umbilical vein endothelial cells (HUVECs) were used for in vitro studies to analyze biological roles.
Results:
The ICP/MAP ratios in the exosome-once and exosome-repeat groups were significantly increased compared to those in the BCNI group. Interestingly, the ICP/MAP ratio showed a greater increase in the exosome-repeat group, which also showed significantly increased smooth muscle/collagen ratio, α-smooth muscle actin and neuronal nitric oxide synthase expression, and cyclic guanosine monophosphate level compared to the BCNI and exosome-once groups. Three genes were significantly differentially expressed in the exosome group, among which Ras homolog family member B promoted cell proliferation and angiogenesis of HUVECs.
Conclusions:
Repeated injections of MSC-derived exosomes can be effective in the treatment of rat models with ED induced by cavernous nerve injury.
... GAPDH was used for standardizing indicated mRNA level [31]. Primers used for qPCR amplification were as follows [32][33][34] ...
Small GTPases regulate multiple important cellular behaviors and their activities are strictly controlled by a mass of regulators. The dysfunction or abnormal expression of small GTPases or their regulators was frequently observed in various cancers. Here, we analyzed the expression and prognostic correlation of several GTPases and related regulators based on the TCGA database and found that Ankyrin Repeat and PH Domain 1 (ARAP1), a GTPase activating protein (GAP), is reduced in lung adenocarcinoma tissues compared to normal tissues and displays a positive correlation with overall survival (OS) and progression-free survival (PFS) of patients with lung adenocarcinoma. qPCR and western blot verified that ARAP1 is frequently downregulated in lung adenocarcinoma tumor tissues and cancer cells, and its downregulation might be mediated by epigenetic modification. Moreover, metastatic assays showed that overexpression of ARAP1 significantly inhibits metastasis of lung adenocarcinoma in vitro and in vivo. We further demonstrated that Rho signaling inhibition, mediated by RhoGAP activity of ARAP1, majorly contributes to suppressing migration and invasion of lung adenocarcinoma cancer cells via inhibiting stress fibers formation. In summary, this study indicates that ARAP1 may serve as a potential prognostic predictor and a metastatic suppressor in lung adenocarcinoma via its RhoGAP activity.
Supplementary Information
The online version contains supplementary material available at 10.1007/s12672-023-00832-x.
... [23][24][25] In lung cancer, RhoB regulated the activity of PP2A to modulate mesenchymal phenotype and invasion. 26,27 Diao et al 28 discovered that RhoB mediated cell proliferation, adhesion and migration in osteoblastic cells. Similarly, Tan et al 29 indicated RhoB suppressed cell growth, migration and induced cell apoptosis in pancreatic cancer. ...
... Furthermore, in lung cancer and osteoblastic cell RhoB mediated cell proliferation, adhesion, migration and invasion in lung cancer and osteoblastic cell. 27,28 In our study, knockdown of miR-19a inhibited osteosarcoma cell EMT through RhoB. However, due to the limited number of cases, the correlation between miR-19a and RhoB expression is low, which is the limit of this experiment. ...
Introduction
Osteosarcoma is the most common bone tumor with high metastasis and recurrence rate. MicroRNA-19a (miR-19a) has been reported to act as tumor oncogene in multiple cancers. The objective of the study was to explore the molecular mechanisms of miR-19a in osteosarcoma cell migration and invasion.
Materials and methods
Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting were employed to measure the levels of miR-19a and RhoB in osteosarcoma tissues and cell lines. Transwell assay was employed to analyze the tissues and cell lines’ migratory and invasive abilities. Dual luciferase reporter assay was utilized to analyze the association between miR-19a and RhoB.
Results
MiR-19a was overexpressed in osteosarcoma tissues and cell lines. MiR-19a promoted osteosarcoma cell migration and invasion in vitro. RhoB was thus confirmed as a direct and functional target of miR-19a, and it could partially reverse the function of miR-19a. Knockdown miR-19a inhibited osteosarcoma cell epithelial-mesenchymal transition (EMT) and suppressed osteosarcoma xenograft growth.
Conclusion
MiR-19a enhanced cell migration, invasion and EMT through RhoB in osteosarcoma. The newly identified miR-19a/RhoB axis provides novel insight into the progression of osteosarcoma and offers a promising target for osteosarcoma therapy.
... Loss of adhesiveness correlates with enhanced tumor cell motility and LY294002 blocked breast cancer cell adhesiveness induced by dexamethasone [58]. Dexamethasone also induced pro-adhesion and anti-migration in MG-63 osteosarcoma cells by upregulating RhoB via the PI3K/Akt pathway [59]. These results are parallel to our findings that low doses of PI3K-inhibitors attenuated antigrowth and antiinvasive actions of dexamethasone on glioma spheroids. ...
