MicroRNA‑92b promotes cell proliferation and invasion in osteosarcoma by directly targeting Dickkopf‑related protein 3
Authors: Hui Li
Yanfei Xiong
Wei Zhou
Xing Liu
Qing Wu
Qiong Feng
Journal: Experimental and Therapeutic Medicine (2017)
Discipline: CLINICAL MEDICINE
Keywords: Dickkopf-related protein 3; invasion; microRNA; osteosarcoma; proliferation.
Affiliations: Department of Orthopedics, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China., Department of Vascular Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China., Nursing School, Nanchang University, Nanchang, Jiangxi 330006, P.R. China., Department of Orthopedics, Jing An Hospital, Yichun, Jiangxi 330600, P.R. China., Department of Immunology and Microbiology, Medical School of Jishou University, Jishou, Hunan 416000, P.R. China.

Abstract:  Deregulation of microRNA-92b (miR-92b) has been implicated in osteosarcoma. However, the underlying regulatory mechanism of miR-92b in osteosarcoma growth and metastasis remains largely unclear. In the present study, reverse transcription-quantitative polymerase chain reaction and western blotting were used to measure mRNA and protein expression. MTT and Transwell assays were conducted to determine cell proliferation and invasion, and a luciferase reporter assay was performed to confirm the association between miR-92b and Dickkopf3-related protein (DKK3). The results demonstrated that miR-92b was significantly upregulated in osteosarcoma tissues compared with matched adjacent non-tumor tissues. Additionally, high miR-92b levels were significantly associated with lung metastasis and advanced tumor, node, metastasis stage (P&lt;0.05) but not with age, sex, tumor size, location, serum lactate dehydrogenase or serum alkaline phosphatase. miR-92b expression was also significantly upregulated in osteosarcoma cell lines compared with normal osteoblast cells. Knockdown of miR-92b significantly inhibited the proliferation and invasion of osteosarcoma U2OS cells (P&lt;0.01). By contrast, overexpression of miR-92b significantly increased U2OS cell proliferation and invasion (P&lt;0.01). DKK3 was identified as a target gene of miR-92b and it was demonstrated that DKK3 expression was negatively regulated by miR-92b in U2OS cells. Restoration of DKK3 expression abrogated the increased proliferation and invasion of U2OS cells induced by miR-92b overexpression. Notably, DKK3 was significantly downregulated in osteosarcoma tissues compared with adjacent non-tumor tissues and its expression was inversely correlated to miR-92b levels in osteosarcoma tissues. Taken together, these data indicate that miR-92b promotes cell proliferation and invasion in osteosarcoma by targeting DKK3. Therefore, miR-92b may become a potential therapeutic target for osteosarcoma. 

Retracted: Yes

PubPeer comments:
 The paper contains a number of claims that can be disproven via a search using pubmed. Examples of such statements are: *there are no true hermaphrodites (i.e. individuals producing both sperm and eggs)* and *no such examples [of simultaneous or sequential hermaphrodites] have ever been observed in mammals* . There have in fact been multiple reports of human individuals that have produced both sperm and eggs. One such [example ] . The individual in question was able to have children (which meets the author s criterion that any additional sex would have to be fertile). An example of a [mammal] : a rabbit that was able to both become pregnant in isolation and sire children of both sexes, demonstrating autofertilisation. Both examples used in this comment were written decades before the paper in question and therefore should have been seen by the author if they had researched the statements quoted beforehand. For a variable to binary there must be 2 and only 2 values, if a 3rd value is observed, even only once, then that variable is by definition not binary (this the only definition of binary used in chemistry, physics, computer science, mathematics...). The paper uses a definition of sex typical of evolutionary biology, that is solely gamete-based: *The type of gametes produced is a very objective criterion for classifying the sex of an individual, and is its fundamental defining feature*. *At the level of gametes, sex in eukaryotes is inherently digitalu2014two gametes fuse together to form one zygote. Yet it need not be binaryu2014more than two mating types can exist*,. [sic]. Therefore, by the paper s own logic, a human s individual sex wouldn t be binary and humans would in fact have 3 sexes with the 3rd sex being hermaphrodites. Additionally the paper contains a number of typos, which could be due to the journal not being peer-reviewed. ,