MicroRNA-330-5p promotes the development of osteosarcoma by regulating SPRY2
Authors: L Qin
R Meng
H-B Li
Q Wei
X-F Han
Q-Q Li
X-C Zhai
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: MicroRNA-330-5p; osteosarcoma; prognosis; clinicopathological parameters; metastasis
Affiliations: Department of Orthopedics, Shanxian Central Hospital, Heze, China. .

Abstract:  Objective: MicroRNA is an endogenous, non-coding small RNA that has a significant role in regulating organisms and pathology. Previous studies have demonstrated that microRNA-330-5p was a cancer-promoting gene. However, the role of microRNA-330-5p in osteosarcoma (OS) has not been reported. The aim of this work was to explore the characteristics of microRNA-330-5p expression in OS, and to further study its expression in OS and its relationship with clinicopathological parameters and prognosis. Patients and methods: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to investigate the expression of microRNA-330-5p in 48 pairs of OS tissues and paracancer tissues, and to analyze the relationship between the expression of microRNA-330-5p and OS clinical indicators and patient prognosis. Meanwhile, qRT-PCR was performed to verify the microRNA-330-5p expression in OS cells. In addition, the microRNA-330-5p knockdown expression model was constructed using lentivirus in OS cell lines U2OS and MG63. The effects of microRNA-330-5p on the biological function of OS cells were analyzed by Cell Counting Kit-8 (CCK-8) and transwell experiments. The potential mechanism was explored by Western blot. Results: In this paper, qRT-PCR results showed that the expression of microRNA-330-5p in OS was higher than that in paracancer tissues, and the difference was statistically significant. Compared with microRNA-330-5p low expression group, patients with high expression of microRNA -330-5p had a higher prevalence of distant metastasis and a lower overall survival rate. In vitro experiment showed that the proliferation, invasion and metastasis abilities of the cells in the microRNA-330-5p silencing group were markedly decreased compared with the negative control group (NC group). Western blot results demonstrated that microRNA-330-5p inhibitor can activate SPRY2 and regulate the expression of key proteins, such as p-Smad2, p-Smad3, TGF-β1, MMP9 and Vimentin in the TGF-β1/Smad signaling pathway. It was found that there was a mutual regulation between microRNA-330-5p and SPRY2, which promoted the malignant progression of OS. Conclusions: The expression of microRNA-330-5p was markedly increased in OS, which was associated with distant metastasis and poor prognosis. Furthermore, we found that microRNA-330-5p may promote the vicious progression of OS by inter-modulating SPRY2 and the TGF-β1/Smad signaling pathways. 

Retracted: No

PubPeer comments:
 [right] Fig 3C from [Wei et al (2019)] .  There was a significant negative correlation with the expression of SPRY2 and the expression of microRNA-330-5p in osteosarcoma tissues. *[left]* Fig 3E from [Shi et al (2019)] .  Negative correlation between expression levels of miR-188-5p and PAPAS. ![file] Remarkable overlap. , 
 Fig 1D.  Kaplan-Meier survival curve of osteosarcoma patients based on microRNA-330-5p expression; the prognosis of patients with high expression was significantly worse than that of the bottom expression group . ![file] Another manifestation of Hoya s Law for J.BUOn and ERMPS...  When 40 or 50 cases of any given cancer are dichotomised into half-groups of high- or low-expression of any given nc-RNA, survival rate for one half-group or both will drop to 0% at 75 months. Other examples, from left to right: - Fig 1 from [Zang et al (2020)] - Fig 1 from [Li et al (2020)] - Fig 1, and Fig 4D, from [Cui et al (2019)] - Fig 1D from [Gao et al (2019)] . ![file] *[left]* Figure 1C from [Wu et al (2020)] . *[right]* Figs 1D, 3E from [Wu et al (2019)] . ![file] , 
 internal plot duplication ![file] possible external plot duplication https: pubmed.ncbi.nlm.nih.gov 30915739 ![file] , 
 #1 The scatterplot belongs within the  subgroup of at least 9 papers that have very similar negative correlation plots [(H t Elisabeth Bik] ): ![] Here is Fig 3C again, with (at right) a superimposition of 11 versions of the scatterplot. Data points are darker if they appear in more versions. ![file] ,