miR-22-Notch Signaling Pathway Is Involved in the Regulation of the Apoptosis and Autophagy in Human Ovarian Cancer Cells

Li, Yan; Gu, Yue; Tang, Na; Liu, Yanqing; Zhao, Zhan-kao

doi:10.1248/bpb.b18-00084

Cited by 18 publications

(13 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MiR‐22 has already been found to act as either a tumor suppressor or an oncomiRNA in different cancers. Recent research found that miR‐22 promotes autophagy of human ovarian cancer cells through the suppression of the Notch signaling pathway. In contrast, we observed miR‐22 to promote osteosarcoma chemoresistance via autophagy repression and stimulation of apoptosis, suggesting that miR‐22 functions in a disease‐specific context.…”

Section: Discussioncontrasting

confidence: 60%

Roles of microRNA‐22 in Suppressing Proliferation and Promoting Sensitivity of Osteosarcoma Cells via Metadherin‐mediated Autophagy

Wang

Zhao

Guo

et al. 2019

Orthopaedic Surgery

View full text Add to dashboard Cite

Objective To analyze the effect of microRNA‐22 on autophagy and proliferation and to investigate the underlying molecular mechanism of osteosarcoma cell chemotherapy sensitivity. Methods MG‐63 cells were divided into four groups, including a control group, a negative control (NC) group, a cisplatin group, and a cisplatin + miR‐22 group. Proliferation of MG‐63 cells that had been treated with cisplatin and transfected with miR‐22 mimics was determined using MTT assay and colony formation assay. We assessed the degree of autophagy using flow cytometry through cellular staining of the autophagy lysosomal marker monodansylcadaverine (MDC). The effect of microRNA‐22 on autophagy was observed along with the expression levels of Beclin1, LC3, metadherin (MTDH) and ATG5 by western blot and quantitative reverse transcription polymerase chain reaction (qRT‐PCR). Luciferase reporter assay revealed the targeted binding site between miR‐22 and the 3′‐untranslated region (3′‐UTR) of MTDH mRNA. Western blot and qRT‐PCR were used to explore the level of MTDH in the control group, the NC group, the cisplatin group, and the miR‐22 group for 6, 12, and 24 h. Results In the in vitro study, the MTT results indicated that the MG‐63 cells with overexpression of miR‐22 exhibited a significant decline in the proliferation capacity compared with the control group (0.513 ± 0.001, P < 0.0005). Similar to the MTT results, MG‐63 cells that were transfected with miR‐22 mimic (101.0 ± 10.58) formed fewer colonies compared with the cisplatin group (129.7 ± 4.163). MDC staining revealed that miR‐22‐overexpressing osteosarcoma (OS) cells treated with cisplatin showed a significant decrease in the expression of autophagy (7.747 ± 0.117, P < 0.0001). Our data revealed that miR‐22 could regulate not only autophagy but also proliferation in the chemosensitivity of osteosarcoma cells. We found that miR‐22 sensitized osteosarcoma cells to cisplatin treatment by regulating autophagy‐related genes. In addition, Luciferase Reporter Assay revealed that miR‐22 negatively regulated autophagy through direct targeting of MTDH. We performed western blot analysis to detect the MTDH expression level. The results revealed that the overexpression of miR‐22 obviously decreased the expression of MTDH (1.081 ± 0.023, P < 0.001). Conclusion Inhibition of miR‐22 ameliorated the anticancer drug‐induced cell proliferation decrease in osteosarcoma cells. MTDH was identified as the miR‐22 target in OS cells and MTDH‐triggered autophagy played a key function in the miR‐22‐associated chemotherapy sensitivity.

show abstract

Section: Discussioncontrasting

confidence: 60%

Roles of microRNA‐22 in Suppressing Proliferation and Promoting Sensitivity of Osteosarcoma Cells via Metadherin‐mediated Autophagy

Wang

Zhao

Guo

et al. 2019

Orthopaedic Surgery

View full text Add to dashboard Cite

show abstract

“…10) circPTN regulates proliferation activity in glioma by targeting miR-145-5p/miR-330-5p. 30) Accumulating evidence points to the potential role of miRNAs in DKD progression. 31) It is reasonable to speculate that circACTR2 may regulate DKD by sponging miRNA or other targets, which encourages continued exploration of circACTR2 in the pathogenesis of DKD.…”

Section: Discussionmentioning

confidence: 99%

circACTR2: A Novel Mechanism Regulating High Glucose-Induced Fibrosis in Renal Tubular Cells <i>via</i> Pyroptosis

et al. 2020

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease. Current therapies for DKD are insufficient. Therefore, there is an urgent need for identifying new therapies. An increasing number of micro RNAs (miRNAs) and long noncoding RNAs (lncRNAs) have been demonstrated to modulate the progression of diabetic kidney disease. Nevertheless, until now, there have been few reports evaluating the relevance of circular RNAs (circRNAs) in DKD. circRNAs have been reported to regulate the occurrence and development of multiple diseases. In this study, we intended to explore the circRNA expression profiles and determine the role of circRNA in DKD. We identified a series of dysregulated circRNAs in glucose-stressed HK-2 cells using circRNA microarray analysis. Among the candidate circRNAs, we found that circACTR2 was upregulated and may be involved in inflammation and pyroptosis. Knockdown of circACTR2 significantly decreased pyroptosis, interleukin (IL)-1β release and collagen IV and fibronectin production, indicating the effective regulation by circACTR2 of cell death and inflammation. Overall, our study identified a new circRNA, circACTR2, that regulates high glucose-induced pyroptosis, inflammation and fibrosis in proximal tubular cells. The present study preliminarily explores the role of circRNAs in pyroptosis of tubular cells, and provides novel insight into the pathogenesis of DKD and new therapeutic strategies.

show abstract

“…The miR-22, a multifunctional molecule and broadly expressed in multitype of tissues in mammals, was found involved in the pathogenesis of many diseases, such as cancer, arthritis, kidney injury, and osteogenic impairment. [15][16][17][18] However, the role of lncRNA-TM1P3/miR-22/ALK1 in cartilage remained unknown, especially their role in ECM degradation and OA pathogenesis. Therefore, the present study was aimed to investigate the interaction of miRNA-22 and lncRNA-TM1P3, which contributed to the overexpression of MMP13 in chondrocyte ECM degradation in the pathogenesis of OA.…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA TM1P3 is involved in osteoarthritis by mediating chondrocyte extracellular matrix degradation

et al. 2019

J of Cellular Biochemistry

View full text Add to dashboard Cite

Background and Objectives: Osteoarthritis (OA) is a widespread degenerative joint disease characterized by articular cartilage degradation and is the leading cause of physical disability. Noncoding RNAs, especially long noncoding RNAs (lncRNAs) and microRNAs, are involved in the degradation of the chondrocyte extracellular matrix (ECM) in patients with OA. The present study was aimed to investigate the effects of lncRNA and miR-22 on the degradation of the chondrocyte ECM and underlying mechanisms. Methods: To simulate conditions found in OA, primary cultured chondrocytes were treated with IL-1, TGF-β, or sb525334. Real-time PCR and Western blot analysis were performed to detect expressions of miR-22, lncRNA-TM1P3, ALK1, MMP13, pSMAD1/5, SMAD1, and pSMAD5. Small interfering RNAs and a miR-22 mimic or inhibitor were utilized to determine lncRNA-TM1P3 knockdown and miR-22 overexpression or inhibition.Results: The lncRNA-TM1P3 significantly upregulated in patients with OA, accompanied by the downregulation of miR-22 and upregulation of pSMAD1/5 and MMP13, which ultimately resulted in the degradation of the chondrocyte ECM in patients with OA. Bioinformatics analysis predicted miR-22 as a target of both lncRNA-TM1P3 and MMP13. The lncRNA-TM1P3 knockdown significantly increased the expression of ALK1, a corresponding increase in ECM degradation was observed by affecting the phosphorylation of SMAD1/5 and the expression of MMP13, which did not affect the expression of ALK1.Conclusions: These findings demonstrated that the lncRNA-TM1P3/miR-22/ TGF-β signaling/MMP13 axis is involved in the degradation of chondrocyte ECM in patients with OA, which could provide novel therapies for OA treatment.

show abstract

miR-22-Notch Signaling Pathway Is Involved in the Regulation of the Apoptosis and Autophagy in Human Ovarian Cancer Cells

Cited by 18 publications

References 33 publications

Roles of microRNA‐22 in Suppressing Proliferation and Promoting Sensitivity of Osteosarcoma Cells via Metadherin‐mediated Autophagy

Roles of microRNA‐22 in Suppressing Proliferation and Promoting Sensitivity of Osteosarcoma Cells via Metadherin‐mediated Autophagy

circACTR2: A Novel Mechanism Regulating High Glucose-Induced Fibrosis in Renal Tubular Cells <i>via</i> Pyroptosis

Long noncoding RNA TM1P3 is involved in osteoarthritis by mediating chondrocyte extracellular matrix degradation

Contact Info

Product

Resources

About