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Objective: This study aimed to explore the miR-1247-mediated promotion of osteosarcoma (OS) cell proliferation by SOX9. Methods: We recruited 97 OS patients admitted to our hospital (the observation group, OG) and 82 healthy people undergoing physical examinations (the control group, CG) over the same period into this study. The expression of miR-1247 and SOX9 in human OS cells in vitro was tested to determine the effect of miR- 1247 and SOX9 on OS and to analyze the relationship between miR-1247 and SOX9. Results: We detected lowly expressed miR-1247 and highly expressed SOX9 in the peripheral blood of OS patients (P < 0.05). Both miR- 1247 and SOX9 showed good performances in diagnosing OS. OS cells (143B cells) in the miR-1247-mimics group showed markedly lower cell proliferation and invasion rates and higher apoptosis rates than cells in the miR-1247-inhibitor group and the miR-NC group (P < 0.05). 143B cells in the sh-SOX9 group showed higher proliferation and invasion rates and lower apoptosis rates than cells in the si-SOX9 group and the NC group (P < 0.05). SOX9 protein concentrations were lower in cells in the miR-1247-mimics group than in cells in the miR-1247-inhibitor group and the miR-NC group (P < 0.05), with higher SOX9 protein concentrations in the miR-1247-inhibitor group than in the miR-NC group (P < 0.05). Conclusion: MiR-1247 is lowly expressed in OS. It can promote the proliferation and invasion of OS cells and accelerate the progression of OS by mediating SOX9. [ABSTRACT FROM AUTHOR]

Lingping Zhu,1,2 Zhiqun Shu,3 Xiaoming Sun2,3 1Department of General Practice, Shenzhen Longhua District Central Hospital, Shenzhen, People’s Republic of China; 2Department of General Practice, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Pudong Institute for Health Development, Shanghai, People’s Republic of China Background: The purpose of this study was to investigate the expression of different miRNAs in nonmetastatic and metastatic endometrial cancer Existing evidence indicates that there are many factors affecting the metastasis of endometrial cancer, and miRNAs play an unique role in many processes of endometiral cancer. Materials and methods: miRNA sequences were downloaded from The Cancer Genome Atlas Project database, and Bioinformatics technique was used to deal with those data. Results: We elucidated the relation between differentially expressed miRNAs and clinical information for a total of 260 tumor tissues and 22 tumor tissues that had metastasized. We used the threshold of P 1.2 to identify potential miRNAs. Four differentially expressed miRNAs were identified in nonmetastatic and metastatic endometrial cancers. Further differential analysis of metastatic tissue revealed that miR-1247 is associated with metastasis of endometrial cancer to the lung, and miR-3200 is associated with the clinical stage of endometrial cancer. A functional enrichment analysis showed that the four miRNAs may be involved in multiple pathways of cancer, including the Wnt, NOTCH, and TGF-β signaling pathways and signaling pathways regulating pluripotency of stem cells. Protein–protein interaction analysis showed that PAK6, SNAP25, MAN1A1, MYB, ZBTB4, UST, ALDH1A3, and NRP2 are hub genes of relevant miRNAs in endometrial cancers. Conclusion: The current study indicates that these four miRNAs may be related to molecular markers of metastasis of endometrial cancer. Keywords: endometrial cancer, bioinformatics, miR-1247, protein analysis

Abstract Background Neuroblastoma (NB) represents the most common extracranial solid tumor in children. Accumulating evidence shows that microRNAs (miRs) play an important role in the carcinogenesis of NB. Here, we investigated the biological function of miR-1247 in NB in vitro. Methods/results We found miR-1247 was downregulated in NB tissues and cells using quantitative PCR analysis. Gain- and loss-of-function studies demonstrated that miR-1247 significantly suppressed cell proliferation and induced cell cycle G0/G1 phase arrest and cell apoptosis of NB cells in vitro by using MTT, colony formation assay and Flow cytometry analysis. Luciferase assay suggested ZNF346 was the target of miR-1247 and its expression could be downregulated by miR-1247 overexpression using Western blotting. Furthermore, downregulation of ZNF346 by siRNA performed similar effects with overexpression of miR-1247 in NB cells. Conclusions Our findings suggested miR-1247 directly targeted to repress ZNF346 expression, thus suppressing the progression of NB, which might be a novel therapeutic target against NB.

OBJECTIVE: Osteosarcoma (OS) is a common malignant bone tumor that poses a serious threat to the health of adolescents or children. A large number of studies have proposed the role of microRNAs (miRNAs) in OS, except for miR-1247. Therefore, this research was designed to explore the molecular mechanism of miR-1247 in OS. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) or Western blot analysis was used to measure the expressions of miR-1247 and genes. The function of miR-1247 was investigated using Cell Counting Kit-8 (CCK-8) and transwell assays. The Dual-Luciferase reporter assay was used to explore the relationship between miR-1247 and neuropilin-1 (NRP1). RESULTS: MiR-1247 was downregulated in OS, which was related to the aggressive behavior of OS patients. Moreover, miR-1247 inhibited cell viability and metastasis in OS. At the same time, miR-1247 promoted apoptosis and inactivated the Wnt/ß-catenin pathway in OS. Furthermore, it was confirmed that NRP1 was a direct target of miR-1247. Upregulation of NRP1 attenuated the inhibitory effect of miR-1247 in OS. CONCLUSIONS: MiR-1247 played a suppressive role in OS by suppressing cell viability and metastasis. [ABSTRACT FROM AUTHOR]

Cancer progression is strictly dependent on the relationship between tumor cells and the surrounding stroma, which supports cancer malignancy promoting several crucial steps of tumor progression, including the execution of the epithelial to mesenchymal transition (EMT) associated with enhancement in cell invasion, resistance to both anoikis and chemotherapeutic treatments. Recently it has been highlighted the central role of microRNAs (miRNAs) as regulators of tumor progression. Notably, in several tumors a strong deregulation of miRNAs is observed, supporting proliferation, invasion, and metabolic reprogramming of tumor cells. Here we demonstrated that cancer‐associated fibroblasts induce a downregulation of miR‐1247 in prostate cancer (PCa) cells. We proved that miR‐1247 repression is functional for the achievement of EMT and increased cell invasion as well as stemness traits. These phenomena contribute to promote the metastatic potential of PCa cells as demonstrated by increased lung colonization in in vivo experiments. Moreover, as a consequence of miR‐1247 downregulation, we observed a correlated increased expression level of neuropilin‐1, a miR‐1247 target involved as a coreceptor in the epidermal growth factor receptor signaling. Taken together, our data highlight miR‐1247 as a potential target for molecular therapies aimed to block the progression and diffusion of PCa. Diagrammatic summary of the molecular basis of miR‐1247 action in prostate cancer (PCa) cells. Cancer‐associated fibroblast (CAF)‐induced miR‐1247 downregulation promotes invasion, stemness, and metastatic dissemination of PC3 cells, thus sustaining tumor progression [ABSTRACT FROM AUTHOR]

Objective This study aimed to explore the potential roles and mechanism of miR-1247 in lipopolysaccharides (LPS)-induced acute pneumonia. Materials and methods The miR-1247 expression in acute stage patients with infantile pneumonia was detected. To establish the cell model of acute pneumonia, A549 cells were treated with 1 mg/mL lipopolysaccharides (LPS). The effects of miR-1247 dysregulation on the cell viability, apoptosis, inflammation and autophagy of LPS-induced A549 cells were investigated. Moreover, the functional targets of miR-1247 were identified and the regulatory relationships between miR-1247 and JNK or NF-κB pathways were explored. Results The miR-1247 was lowly expressed in acute phage patients with infantile pneumonia. In addition, LPS treatment significantly inhibited A549cell viability, induced apoptosis, promoted the production of cytokines and decreased autophagy, thus causing A549 cell injury. Moreover, miR-1247 was decreased expression after LPS treatment, and overexpression of miR-1247 alleviated LPS-induced A549 cell injury. Furthermore, CC chemokine ligand (CCL) 16 was a functional target gene of miR-1247. Knockdown of CCL16 alleviated LPS-induced cell injury, and the combination of miR-1247 inhibition and CCL16 knockdown reversed the effects of CCL16 knockdown alone on LPS-induced A549 cell injury. Besides, inhibition of miR-1247 activated JNK and NF-κB pathways, while knockdown of CCL16 inhibited the activation of these pathways. Conclusions Our data reveals that miR-1247 is lowly expressed in acute stage patients with infantile pneumonia. Overexpression of miR-1247 may alleviate LPS-induced A549 cell injury through targeting CCL16. JNK and NF-κB pathways may be key mechanisms to regulate the role of miR-1247 in LPS-induced lung injury. [ABSTRACT FROM AUTHOR]

Recently, microRNA-1247 (miR-1247) has been reported to function as tumour suppressor in several cancer types, including pancreatic cancer, hepatocellular cancer and lung cancer. However, the biological function of miR-1247 in bladder cancer and the underlying mechanisms have remained largely uncovered. In this study, the expression of miR-1247 was significantly downregulated, while RAB36 protein was remarkably upregulated in bladder cancer tissues and cell lines compared with that in paired adjacent normal tissues or normal cell line (SU-HUC-1). The function of miR-1247 and RAB36 in the cell viability, proliferation and invasion of bladder cancer cells (T24 and J82) was assessed by CCK-8, colony formation and Transwell assay, respectively. Gain of function studies showed that upregulation of miR-1247 significantly inhibited cell proliferation and invasion capacity of bladder cancer cells. Consistently, downregulation of RAB36 mimicked the suppressive effects of miR-1247 overexpression in bladder cancer cells. Importantly, miR-1247 was confirmed to target the 3′untranslated region (UTR) of RAB36 and downregulated its expression using luciferase reporter assay and Western blot assays. In conclusion, these results provide the first clues regarding the role of miR-1247 might be a potential therapeutic agent and diagnostic marker of bladder cancer by inhibiting RAB36 expression. [ABSTRACT FROM AUTHOR]

Excessive alcohol consumption has a significant impact on human health and is a major public health problem worldwide. One of the consequences of long-term excessive alcohol consumption is cellular injury in almost all organs and tissues, with acute kidney injury (AKI) being one of the most common pathological manifestations. In the present study, using a mouse model of alcoholic liver fibrosis-associated AKI induced by a combined treatment with carbon tetrachloride (CCl 4 ) and ethanol and resembling pathological features of AKI in human alcoholic liver fibrosis, we demonstrate alterations in histone modifications in the kidneys and, importantly, in the promoter region of the over-expressed SRY (sex determining region Y)-box 9 ( Sox9 ) gene. The level of SOX9 protein in the kidneys of AKI-mice is reduced and correlates inversely with increased expression of microRNA miR-1247. Mechanistically, the over-expression of miR-1247 is associated with a markedly increase in histone H3 lysine 4 trimethylation in the upstream region of the Mir1247 gene. The results of the present study demonstrate a functional role of epigenetic mechanisms in AKI and indicate the importance of correcting the epigenetic dysregulation for proper renal tubule maintenance and repair. [ABSTRACT FROM AUTHOR]

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. Panel “Control” from Figure 3C appears similar to panel “si-PVT1” from Figure 2A of the article that Wei Huang, Xiuwen Lan, Xueting Li, Dawei Wang, Yinghao Sun, Qian Wang, Hong Gao and Kaijiang Yu have published in the International Immunopharmacology 47 (2017) 134–140 https://doi.org/10.1016/j.intimp.2017.03.030, panel “Control” from Figure 2D of the article that Xiaodi Liu, Chengying Hong, Shipin Wu, Shiling Song, Zhi Yang, Lin Cao, Tongwei Song and Ying Yang have published in the Journal of Cellular Biochemistry 120 (2019) 11331–11341 https://doi.org/10.1002/jcb.28409 and panel “LPS+sh-NEAT1” from Figure 2C of the article that Chen Yi, Qiu Jialing, Chen Bin, Lin Youping, Chen Yulan, Xie Guojin, Qiu Junming, Tong Huasheng and Jiang Dongxin have published in the International Immunopharmacology 59 (2018) 252–260 https://doi.org/10.1016/j.intimp.2018.03.023. Moreover, panel “Control” from Figure 5C appears similar to panel “Control” from Figure 2A of the article from the International Immunopharmacology 47 (2017) 134. Given the comments of Dr Elisabeth Bik https://scienceintegritydigest.com/2020/02/21/the-tadpole-paper-mill/ regarding this article, the journal requested the corresponding author to provide the raw data. However, the author was not able to fulfil this request., (Copyright © 2018. Published by Elsevier Masson SAS.)

Altered expression of microRNAs has been strongly implicated in human cancers, and growing evidence is emerging that a number of miRNAs are downregulated in cancer associated with CpG island hypermethylation. Although pancreatic cancer is one of the most malignant human cancers, the roles of miRNAs underlying the tumorigenesis of pancreatic cancer are still poorly understood. In the present study, we explored the molecular functional role of microRNA-1247 as tumor suppressor associated with epigenetic alteration in pancreatic cancer. CpG islands methylation of miR-1247 is frequently observed in various pancreatic cancer cell lines and in primary pancreatic tumors, but not in normal pancreatic tissue. Ectopic expression of miR-1247 in five pancreatic cancer cell lines results in suppressing of cell growth, proliferation, migration, and invasion in vitro and tumorigenicity of pancreatic cancer cells in vivo. Interestingly, we found one putative target gene of miR-1247, regulator of chromosome condensation 2 (RCC2), harbored miR-1247 target sequences in the 3' UTR of its mRNA. In functional studies in vitro to understand the interaction between miR-1247 and RCC2, decreasing of RCC2 gene expression by miR-1247 was observed by immunoblotting and immunohistochemistry at both mRNA and protein levels. Moreover, luciferase reporter assay confirmed that RCC2 was a direct target of miR-1247. Taken together, our data suggest that CpG island hypermethylation of miR-1247 is responsible for its downregulation in pancreatic cancer, and ectopic expression of miR-1247 functions as a potential tumor suppressor targeting RCC2 in pancreatic cancer cells.

microRNAs (miRNA) are regulators of gene expression, but little is known about miRNA expression profiles in stem cells of osteosarcoma (OS). C117 and Stro-1 are known stem cell markers of OS. In the study, CD117 and stro-1 positive (CD117(+)stro-1(+)) and CD117 and stro-1 negative (CD117(-)stro-1(-)) cells were isolated from MG63 cells CD117(+)stro-1(+) cells showed more metastatic ability and stem cell formation rate than CD117(-)stro-1(-) ones. To find the difference between CD117(+)stro-1(+) and CD117(-)stro-1(-) cells, the miRNA expression profile was examined using DNA microarray. MicroRNAs were differentially expressed in osteosarcoma cells with CD117(+)stro-1(+) and CD117(-)stro-1(-). The significant miRNAs included miR-15a, miR-302a, miR-423-5p, miR-1247, miR-1243 and others, which were confirmed by real time RT-PCR. The significant down-regulated miR-1247 was confirmed that was a potential tumor suppressor by targeting MAP3K9. Our results indicated that dysregulation of miRNAs is involved in osteosarcoma and miR-1247 plays an important role in progression of osteosarcoma.