RGS16 regulated by let-7c-5p promotes glioma progression by activating PI3K-AKT pathway / 医学前沿

Gliomas are the most common central nervous system tumours; they are highly aggressive and have a poor prognosis. RGS16 belongs to the regulator of G-protein signalling (RGS) protein family, which plays an important role in promoting various cancers, such as breast cancer, pancreatic cancer, and colorectal cancer. Moreover, previous studies confirmed that let-7c-5p, a well-known microRNA, can act as a tumour suppressor to regulate the progression of various tumours by inhibiting the expression of its target genes. However, whether RGS16 can promote the progression of glioma and whether it is regulated by miR let-7c-5p are still unknown. Here, we confirmed that RGS16 is upregulated in glioma tissues and that high expression of RGS16 is associated with poor survival. Ectopic deletion of RGS16 significantly suppressed glioma cell proliferation and migration both in vitro and in vivo. Moreover, RGS16 was validated as a direct target gene of miR let-7c-5p. The overexpression of miR let-7c-5p obviously downregulated the expression of RGS16, and knocking down miR let-7c-5p had the opposite effect. Thus, we suggest that the suppression of RGS16 by miR let-7c-5p can promote glioma progression and may serve as a potential prognostic biomarker and therapeutic target in glioma.

A study on the protective mechanisms of lipoxin A4 for hyperoxia-induced pulmonary epithelial cells injury in mice / 中国新生儿科杂志

Objective To study the protective mechanisms of lipoxin A 4 ( LXA4 ) for hyperoxia-induced lung injury through modulation of let-7c/TGF-β1 signal pathway in mice.Method MLE-12 cells was transfected with let-7c mimic, mimic negative control ( NC) , let-7c inhibitor and inhibitor NC.The cells were assigned into hyperoxia group , LXA4 group, let-7c over-expression group, let-7c silence group, let-7c silence+LXA4 group, and all exposed to 85% oxygen.The mRNA level of the extracellular matrixα-smooth muscle actin (α-SMA) and collagen Ⅰ( COL-Ⅰ) , and the expression of related genes in TGF-β1 signaling pathway (Smad 2, Smad 3, Smad 4, TGF-βR1, TGF-βR2) were examined using qPCR.The protein expressions in TGF-β1 signaling pathway was examined using Western blot .Result The mRNA expressions of α-SMA, COL-Ⅰ, Smad 3, Smad 4, TGF-βR1 and TGF-βR2 in LXA4 group [(24.3 ±2.1), (14.6 ±0.2), (17.0 ±0.0), (14.9 ±0.1), (20.8 ±0.1), (9.0 ±0.0) ] and let-7c over-expression group [ ( 12.2 ±0.5 ) , ( 3.0 ±0.0 ) , ( 3.1 ±0.0 ) , ( 9.6 ±0.4 ) , ( 28.5 ±0.2 ) , ( 7.6 ± 0.1)] were decreased comparing with the hyperoxia group [(51.4 ±0.5), (32.0 ±0.1), (40.6 ±0.2), (16.3 ±0.1), (89.1 ±1.1), (19.3 ±0.2)].These expressions were increased in both let-7c silence group [(87.3 ±7.0), (38.5 ±0.3), (48.0 ±0.2), (56.5 ±0.2), (126.0 ±0.9), (33.1 ±1.0)] and let-7c silence +LXA4 group [(144.5 ±12.9), (86.3 ±3.0), (91.5 ±4.7), (86.5 ±3.3), (109.0 ±4.5), (45.6 ±1.6)].The protein levels of Smad 2, Smad 3, Smad 4, p-Smad 2, p-Smad 3 and TGF-βR1 of LXA4 group and let-7c over-expression group were decreased comparing with the hyperoxia group, while p-Smad 2, p-Smad 3 of let-7c silence+LXA4 group were increased(P<0.05).Conclusion LXA4 may play a protective role through let-7c /TGF-β1 signal pathway of lung epithelial cells for hyperoxia-induced lung injury in mice .

Anti-inflammatory role of microRNA let-7c in LPS treated alveolar macrophages by targeting STAT3

Objective: To explore the expression of microRNA (miRNA) let-7c and its function in chronic obstructive pulmonary disease (COPD) and alveolar macrophage cells. Methods: Real time PCR was performed to detect the expression of miRNA let-7c in the lung tissue of COPD patients and COPD model in mice. MiRNA let-7c was overexpressed in alveolar macrophages isolated from mice and its effect was measured by the production of pro-inflammation cytokines and the protein level of signal transducer and activator of transcription 3 (STAT3) as well as phosphorylation level of STAT3 after LPS stimulation. Luciferase assay was used to detect the binding of miRNA let-7c and 3'UTR of STAT3. Results: MiRNA let-7c expression was significantly lower in patients with COPD compared with control group, and the similar result was found in COPD mice and LPS stimulated alveolar macrophages. Overexpression of miRNA let-7c in alveolar macrophages inhibited LPS-induced increasing of tumor necrosis factor alpha, interleukin-6 and interleukin-1β. Luciferase assay showed STAT3 was a targeting of miRNA let-7c in alveolar macrophages. Conclusions: MiRNA let-7c low expression in COPD can regulate inflammatory responses by targeting STAT3 in alveolar macrophage, which may provide a new target for COPD treatment strategies.

Anti-inflammatory role of microRNA let-7c in LPS treated alveolar macrophages by targeting STAT3

OBJECTIVE@#To explore the expression of microRNA (miRNA) let-7c and its function in chronic obstructive pulmonary disease (COPD) and alveolar macrophage cells.@*METHODS@#Real time PCR was performed to detect the expression of miRNA let-7c in the lung tissue of COPD patients and COPD model in mice. MiRNA let-7c was overexpressed in alveolar macrophages isolated from mice and its effect was measured by the production of pro-inflammation cytokines and the protein level of signal transducer and activator of transcription 3 (STAT3) as well as phosphorylation level of STAT3 after LPS stimulation. Luciferase assay was used to detect the binding of miRNA let-7c and 3'UTR of STAT3.@*RESULTS@#MiRNA let-7c expression was significantly lower in patients with COPD compared with control group, and the similar result was found in COPD mice and LPS stimulated alveolar macrophages. Overexpression of miRNA let-7c in alveolar macrophages inhibited LPS-induced increasing of tumor necrosis factor alpha, interleukin-6 and interleukin-1β. Luciferase assay showed STAT3 was a targeting of miRNA let-7c in alveolar macrophages.@*CONCLUSIONS@#MiRNA let-7c low expression in COPD can regulate inflammatory responses by targeting STAT3 in alveolar macrophage, which may provide a new target for COPD treatment strategies.

Expression of Let-7c in invasive ductal carcinoma of breast cancer and its clinical significance / 第二军医大学学报

Objective: To investigate the expression of Let-7c in patients with invasive ductal carcinoma of the breast cancer and its correlation with the clinicopathologic features of the patients. Methods: The expression of Let-7c was examined in 40 tissues of invasive ductal carcinoma of the breast cancer and their matched non-tumor adjacent tissue specimens by stem-loop real-time RT-PCR. The correlation of the expression with the clinicopathological features of breast cancer, such as the clinical staging, lymphatic metastasis, and proliferation index, was analyzed. Results: The stem-loop realtime RT-PCR was sensitive and specific in detecting Let-7c expression. Expression of Let-7c in breast cancer tissues was significantly lower than that in the adjacent normal tissues (P10%) (P=0.030) and the status of Estrogen/Progesterone receptor (P=0.040/0.034) in breast cancer patients. There was no significant association of Let-7c expression with menopause condition, breast cancer TNM clinical stage, or lymphatic metastasis(P>0.05). Conclusion: Our results suggest Let-7c may play an important role in the development of breast cancer and the level of Let-7c expression may be a potential parameter in forecasting the progression and prognosis of breast cancer patients.