Knockdown of microRNA-181a inhibits osteosarcoma cells growth and invasion through triggering NLRP3-dependent pyroptosis
Authors: J Li
Z-J Wang
Z Hua
B-G Tian
Journal: European Review for Medical and Pharmacological Sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: miRNA-181a; osteosarcoma; carcinogenesis; molecular mechanism; cell proliferation
Affiliations: Department of Orthopedics, Wuxi traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi, Jiangsu, China. .

Abstract:  Objective: This study aimed to investigate the physiological function and molecular mechanism of microRNA-181a (miRNA-181a) in the carcinogenesis of osteosarcoma. Materials and methods: The relative expression of miRNA-181a in tissues and cultured cells was detected by quantitative real time-polymerase chain reaction (qRT-PCR). MiR-181a inhibitor and miR-181a mimics were used to manipulate its level in cells. Cell proliferation and invasion were measured using Cell Counting Kit-8 (CCK-8) assay and transwell assay, respectively. The protein levels of the targeted genes were detected by Western blotting and immunohistochemistry. Terminal Deoxynucleotidyl Transferase (TdT)-mediated dUTP Nick-End Labeling (TUNEL) assay was employed to detect cell apoptosis. Moreover, a xenograft tumor bearing mice model was used to evaluate the effect of miR-181a in vivo. Results: We found that miRNA-181a was aberrantly elevated in osteosarcoma tissues and cells. Moreover, the overexpression of miRNA-181a could facilitate cell proliferation and migration. By contrast, miRNA-181a knockdown reverses these effects. Additionally, downregulation of miRNA-181a could activate NOD-like receptor protein 3 (NLRP3)-dependent pyroptosis, as evidenced by the increase of pyroptosis-related genes (NLRP3, caspase-1, interleukin-18, and interleukin-1β) in miRNA-181a inhibitor transfected cells compared with the control. Further mechanistic studies identified that miRNA-181a knockdown suppresses cell proliferation and invasion by activating NLRP3-dependent pyroptosis. Silencing NLRP3 could effectively reverse the effects mediated by miRNA-181a inhibitor. Consistently, in vitro results also demonstrated that blockade of miRNA-181a notably suppresses tumor growth via activating pyroptosis. Conclusions: These results provide that miRNA-181a might serve as potential therapeutic target for osteosarcoma patients. 

Retracted: Yes

PubPeer comments:
 Recently [depublished with little explanation] :  The article u201cKnockdown of microRNA-181a inhibits osteosarcoma cells growth and invasion through triggering NLRP3-dependent pyroptosis, by B.-G. Tian, Z. Hua, Z.-J. Wang, J. Li, published in Eur Rev Med Pharmacol Sci 2020; 24 (3): 1030-1040u2013DOI: 10.26355 eurrev_202002_20153u2013PMID: 32096182u201d has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause. Figure 5D may provide the missing explanation:  Downexpression of miRNA-181a suppresses tumor growth in vivo. D, Abundance of Ki-67, PCNA, NLRP3, cleaved caspase-1, IL-1u03b2 and IL-18 in tumor tissues were detected by IHC . ![file] Individual panels here appeared in a long list of otherwise-unrelated papers: for instance, Fig 5C of [Chen, Qi Wu (2018)] and 8D of [Li et al (2019)] : ![] ,