MicroRNA-221 promotes cisplatin resistance in osteosarcoma cells by targeting PPP2R2A
Authors: Yan Liu
Yan-Yan Qu
Chun-Wei Xu
Chen Yang
Hui-Hao Chen
Wen-Chao Yu
Journal: Bioscience reports (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: PPP2R2A; cisplatin; microRNA-221; osteosarcoma cells.
Affiliations: Department of Orthopedic Surgery, Changzheng Hospital, Shanghai 200003, China., Center for Community Health Service, Sub-District of West Nanjing Road, Jing An District, Shanghai, China., Department of Pathology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou 350014, China., Department of Orthopedic Surgery, Changzheng Hospital, Shanghai 200003, China  .

Abstract:  Osteosarcoma (OS), the most common malignant bone tumor, is the main cause of cancer-related deaths in children and young adults. Despite the combination of surgery and multi-agent chemotherapy, patients with OS who develop resistance to chemotherapy or experience recurrence have a dismal prognosis. MicroRNAs (miRNAs) are a class of small noncoding RNAs that repress their targets by binding to the 3'-UTR and/or coding sequences, leading to the inhibition of gene expression. miR-221 is found to be up-regulated in tumors when compared with their matched normal osteoblast tissues. We also observed significant miR-221 up-regulation in the OS cell lines, MG-63, SaoS-2, and U2OS, when compared with the normal osteoblast cell line, HOb. Overexpression of miR-221 promoted OS cell invasion, migration, proliferation, and cisplatin resistance. MG-63 and SaoS-2 cells transfected with miR-221 mimics were more resistant to cisplatin. The IC50 of MG-63 cells transfected with control mimics was 1.24 μM. However, the IC50 of MG-63 cells overexpressing miR-221 increased to 7.65 μM. Similar results were found in SaoS-2 cells, where the IC50 for cisplatin increased from 3.65 to 8.73 μM. Thus, we report that miR-221 directly targets PP2A subunit B (PPP2R2A) in OS by binding to the 3'-UTR of the PPP2R2A mRNA. Restoration of PPP2R2A in miR-221-overexpressing OS cells recovers the cisplatin sensitivity of OS cells. Therefore, the present study suggests a new therapeutic approach by inhibiting miR-221 for anti-chemoresistance in OS. 

Retracted: No

PubPeer comments:
 Another paper has similarities https: pubpeer.com publications A425BAA81AF4CA3AC945CA5430260E#3 , 
 Sorry for our late response. unfortunately, Pubpeer is filtered in Iran and we must use VPN to get access to it. 1) Table 1 is identical to table 1 of Barani et al, ACS Omega, 2021. Response: We use the molecular modeling especially molecular dynamic simulation in these works to portrait the drug-niosomes bilayer at atomic level. However, lack of sufficient hardware facilities leads us to simulate a part of niosomes interacting with a number of drugs in the simulation box. The model of niosomes bilayers that we set up in both paper is the same and it contains a 35:35:30 molar ratio of soan60:tween60:ergostrole. However, the structural analysis of the bilayer, including bilayer APL and bilayer thickness have the same values (even with separate analysis) in both paper which prove the reproducibility of our data. 2) The free MTX curve in Figure 7 is more similar than expected (especially given that these are very different molecules) to the free DFX curve shown in Fig 5 of Barani et al, ACS Omega, 2021. Response: For the release behavior of both studies, we used the same dialysis bag with the same pore size. By the way, two studies showed different results. For example, after 1 hr MTX released 22% and DFX 25 % and so on up to MTX 96.1% and DFX 95.2% that is the end of the analysis. 3) Table 3 in both papers has signs   instead of commas in numbers. Response: The u201c u201d is because of the different language of authors and publishers and is not a big deal that is u201c.u201d 4) Furthermore, although the results are supposed to represent different kinetic models, the equations are linear in all cases. The text mentions (in both cases) an  exponent but there is no one in the equations. Response: u201cnu201d is the Diffusion or release exponent that is estimated from linear regression of log ( Mt M ) versus log t. For release data, we obtain all data from the estimated linear regression of each kinetic. Based on KORSMEYER-PEPPAS EQUATION we obtained u2018nu2019 . Korsmeyer u2013 peppas equation is: F = (Mt M ) = Km tn Where: F = Fraction of drug released at time u2018tu2019 Mt = Amount of drug released at time u2018tu2019 M = Total amount of drug in dosage form Km = Kinetic constant n = Diffusion or release exponent t = Time in hours *If you have further questions, please reach me at mahmoodbarani7@gmail.com. ,