[Retracted] Expression and function of PIM kinases in osteosarcoma.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that (in addition to overlapping data panels internally within the figure, suggesting that some of the data had been derived from the same original sources where the results of differently performed experiments were intended to have been portrayed) certain of the data featured in Fig. 5A on p. 2123 had already been published in another article written by different authors at different research institutes [Tian F, Ding D and Li D: Fangchinoline targets PI3K and suppresses PI3K/AKT signaling pathway in SGC7901 cells. Int J Oncol 46: 2355­2363, 2015]. Owing to the fact that the contentious data in the above article had already been published prior to its submission to International Journal of Oncology, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 49: 2116­2126, 2016; DOI: 10.3892/ijo.2016.3708].

circHIPK3 promotes proliferation and migration and invasion via regulation of miR­637/HDAC4 signaling in osteosarcoma cells.

Accumulating evidence has indicated that circular RNAs (circRNAs) serve crucial roles in the progression of a diverse range of different types of cancer, including osteosarcoma (OS). The present study determined the expression pattern and function of circRNA homeodomain interacting protein kinase 3 (circHIPK3), a novel circular RNA, in OS. It was revealed that circHIPK3 expression was upregulated in OS tissue samples and OS cell lines. A localization assay revealed that circHIPK3 was primarily located in the cytoplasm. Using loss­of­function proliferation and Transwell assays, the present study revealed that circHIPK3­knockdown suppressed OS cell proliferation, migration and invasion. Furthermore, the present study screened potential microRNAs that may interact with circHIPK3. It was revealed that microRNA­637 (miR­637) expression was downregulated in OS according to a Gene Expression Omnibus data analysis. In addition, the present study demonstrated that miR­637 expression was downregulated in OS cell lines. A fluorescence in situ hybridization assay revealed that both miR­637 and circHIPK3 were located in the cytoplasm. An in­depth mechanism investigation demonstrated that circHIPK3 expression was inversely correlated with miR­637 expression, and that circHIPK3 was a target of miR­637. In addition, it was revealed that histone deacetylase 4 (HDAC4) was another downstream target gene of miR­637, as demonstrated using a luciferase assay. It was revealed that miR­637 suppressed OS cell proliferation, migration and invasion via targeting of HDAC4. Finally, the present study demonstrated that circHIPK3 sponged miR­637 to promote HDAC4 expression and OS cell proliferation, migration and invasion. In conclusion, the present study uncovered the role of the circHIPK3/miR­637/HDAC4 axis in OS cell proliferation, migration and invasion. It was demonstrated that circHIPK3 promoted OS cell proliferation, migration and invasion by modulating miR­637/HDAC4 signaling.

Long noncoding RNA DANCR, working as a competitive endogenous RNA, promotes ROCK1-mediated proliferation and metastasis via decoying of miR-335-5p and miR-1972 in osteosarcoma.

BACKGROUND: Accumulating evidences indicate that non-coding RNAs (ncRNAs) including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) acting as crucial regulators in osteosarcoma (OS). Previously, we reported that Rho associated coiled-coil containing protein kinase 1 (ROCK1), a metastatic-related gene was negatively regulated by microRNA-335-5p (miR-335-5p) and work as an oncogene in osteosarcoma. Whether any long non-coding RNAs participate in the upstream of miR-335-5p/ROCK1 axial remains unclear. METHODS: Expression of differentiation antagonizing non-protein coding RNA (DANCR) and miR-335-5p/miR-1972 in osteosarcoma tissues were determined by a qRT-PCR assay and an ISH assay. Osteosarcoma cells' proliferation and migration/invasion ability changes were measured by a CCK-8/EDU assay and a transwell assay respectively. ROCK1 expression changes were checked by a qRT-PCR assay and a western blot assay. Targeted binding effects between miR-335-5p/miR-1972 and ROCK1 or DANCR were verified by a dual luciferase reporter assay and a RIP assay. In vivo experiments including a nude formation assay as well as a CT scan were applied to detect tumor growth and metastasis changes in animal level. RESULTS: In the present study, an elevated DNACR was found in osteosarcoma tissue specimens and in osteosarcoma cell lines, and the elevated DNACR was closely correlated with poor prognosis in clinical patients. Functional experiments illustrated that a depression of DANCR suppressed ROCK1-mediated proliferation and metastasis in osteosarcoma cells. The results of western blot assays and qRT-PCR assays revealed that DANCR regulated ROCK1 via crosstalk with miR-335-5p and miR-1972. Further cellular behavioral experiments demonstrated that DNACR promoted ROCK1-meidated proliferation and metastasis through decoying both miR-335-5p and miR-1972. Finally, the outcomes of in vivo animal models showed that DANCR promoted tumor growth and lung metastasis of osteosarcoma. CONCLUSIONS: LncRNA DANCR work as an oncogene and promoted ROCK1-mediated proliferation and metastasis through acting as a competing endogenous RNA (ceRNA) in osteosarcoma.

Expression and function of PIM kinases in osteosarcoma.

The provirus integrating site Moloney murine leukemia virus (PIM) family of serine/threonine protein kinases is composed of three members, PIM1, PIM2 and PIM3, which have been identified as oncoproteins in various malignancies. However, their role in osteosarcoma (OS) remains largely unknown. This study aimed to examine the expression patterns and the clinical significance of PIM kinases in human OS and their biological effects in human OS cell lines. Immunohistochemical staining was used to detect PIM kinases in archived pathologic material from 43 patients with primary OS; in addition, the effects of PIM knockdown and overexpression on the proliferation, migration and invasion of OS cell lines were determined. We observed that all three PIM kinases were frequently expressed in OS, but only PIM1 positive expression was associated with poorer prognosis regarding overall survival of OS patients. In addition, knockdown of PIM kinases notably inhibited OS cell proliferation, migration and invasiveness, whereas overexpression of PIM kinases resulted in increased OS cell growth and motility. This study suggests that PIM1 could be a valuable prognostic marker in patients with OS, and the biological functions of PIM kinase family in the osteosarcoma cell lines indicate that they could serve as potential therapeutic targets for OS.