MicroRNA‚Ä?43 inhibits proliferation, invasion and induces apoptosis of glioblastoma cells by directly targeting ADAM9
Authors: Xiejun Zhang
Weiping Li
Tao Ji
Journal: Molecular Medicine Reports (2017)
Discipline: CLINICAL MEDICINE
Keywords: Glioma; microRNAs; GBM; miR-543; ADAM9
Affiliations: Department of Neurosurgery, Shenzhen Second People's Hospital, Clinical College of Anhui Medical University, Shenzhen, Guangdong 518035, P.R. China.

Abstract:  Glioma is the most common type of malignant brain tumor in humans and accounts for 81% of all malignant brain tumor cases in adults. The abnormal expression of microRNAs (miRs) has been reported to be important in the formation and progression of various types of human cancer, including glioblastoma (GBM). Therefore, studies into the expression, and roles of microRNAs as diagnostic and prognostic markers, as well as their therapeutic value for patients with GBM are warranted. The expression and roles of miR‚Ä?43 have been reported in several types of human cancer. However, the role of miR‚Ä?43 in GBM remains unclear. In the current study, the expression pattern of miR‚Ä?43 in GBM, the effects of miR‚Ä?43 on GBM cells and the underlying molecular mechanism was determined. The results of the present study demonstrated that miR‚Ä?43 was significantly downregulated in GBM tissue samples and cell lines. Furthermore, the upregulation of miR‚Ä?43 inhibited GBM cell proliferation and invasion, as well as promoted cell apoptosis. In addition, a disintegrin and metalloproteinase 9 (ADAM9) was identified to be a direct target gene of miR‚Ä?43. Furthermore, ADAM9 was significantly upregulated in GBM tissue samples and its expression was inversely correlated with miR‚Ä?43 expression in GBM tissue, suggesting that miR‚Ä?43 downregulation may contribute to ADAM9 upregulation in GBM. Finally, the results of the rescue experiment indicated that ADAM9 overexpression significantly reversed the effects of miR‚Ä?43 on the proliferation, invasion and apoptosis of GBM cells, suggesting that miR‚Ä?43 serves as a tumor suppressor in GBM through ADAM9 regulation. Overall, these findings indicate that the miR‚Ä?43/ADAM9 signaling pathway may provide as a potential therapeutic strategy for GBM. 

Retracted: No

PubPeer comments:
 Figs 2G,H and 4G,H.  Apoptotic rate of U87 and U251 cells transfected with miR-543 mimics or NC were measured using flow cytometry analysis and compared with that of the cells involving NC ;  Flow cytometry analysis of U87 and U251 cells transfected with NC, miR-543 mimics or miR-543 mimics+pcDNA3.1-ADAM9. *P 0.05 compared with NC and miR-543 mimics+pcDNA3.1-ADAM9 .  At least three panels appear in other papers by unrelated groups of authors. Orange rectangles: see Figs 2D, 5D, 6D from [Zhao et al (2018)] .  Here in context:  Bright green rectangles: see Figs 2D, 5D from [Hu et al (2018)] .  Here in context:  Blue-grey rectangles: see Figs 2D, 5D from [Liu et al (2017)] .  Here in context:  There may be other matches. , 
 Figs 2G,H and 4G,H again.  Two panels shared with Figs 2D, 6D of [Lv et al (2019)] .  -------------------------------------------- Here in context.  , 
 *[above]* Fig 4C from  MicroRNAu2011139 targets fibronectin 1 to inhibit papillary thyroid carcinoma progression ([Ye et al 2017] ). *[middle]* Fig 5D,E. *[below]* Fig 2C from  MicroRNAu2011584 inhibits cell proliferation and invasion in nonu2011small cell lung cancer by directly targeting MTDH ([Zhang et al 2017] ).  Overlaps marked. Must credit ImageTwin. , 
 *[above]* Fig 2E F. *[below]* Fig 5C from  MicroRNAu2011433 reduces cell proliferation and invasion in nonu2011small cell lung cancer via directly targeting E2F transcription factor 3 ([Liu et al 2018] ).  Unexpectedly overlapping panels. , 
 *[top row]* Fig 4C from  MicroRNAu2011139 targets fibronectin 1 to inhibit papillary thyroid carcinoma progression ([Ye et al 2017] ). *[2nd row]* **Fig 5D,E**. *[3rd row]* Fig 5D from  MicroRNAu2011548b inhibits proliferation and invasion of hepatocellular carcinoma cells by directly targeting specificity proteinufffd1 ([Qiu et al 2019] ). *[4th row]* Fig 5C from  MicroRNAu2011760 inhibits cell proliferation and invasion of colorectal cancer by targeting the SP1u2011mediated PTEN AKT signalling pathway ([Li et al 2017] ). Blue, red, purple, green boxes mark all the pairs and triplets of duplicated panels.  , 
 #3 *[above]* Fig 4C again *[below]* Fig 5C from  MicroRNA-584 inhibits cell proliferation and invasion in non-small cell lung cancer by directly targeting MTDH ([Zhang et al 2017] ).  ------------------------------ The same authors also published  microRNAu2011205 acts as a tumor suppressor and directly targets YAP1 in glioma ([Ji et al 2017] ). ,