[Retracted] MicroRNA­758 inhibits tumorous behavior in tongue squamous cell carcinoma by directly targeting metadherin.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the Transwell invasion assay data shown in Fig. 5E were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes, several of which have already been retracted. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 19: 1883­1890, 2019; DOI: 10.3892/mmr.2019.9805].

Increased expression of cyclooxygenase-2 in synovium tissues and synovial fluid from patients with knee osteoarthritis is associated with downregulated microRNA-758-3p expression.

Cyclooxygenase-2 (COX-2) is a common factor in inflammation, and its specific regulatory mechanism has not been fully elucidated. The present study aimed to investigate COX-2 mRNA and protein expression levels in synovium tissues and synovial fluid from patients with knee osteoarthritis (KOA), and determine the molecular mechanism by which microRNA (miRNA/miR)-758 regulates KOA via COX-2. A total of 37 patients with KOA and 29 patients with acute knee trauma (control group) were enrolled in the present study. Reverse transcription-quantitative PCR analysis was performed to detect miR-758-3p and COX-2 mRNA expression, while western blotting and ELISA were performed to detect COX-2 protein expression in synovium and synovial fluid, respectively. The dual-luciferase reporter assay was performed to verify the interaction between miR-758-3p and the 3'-untraslated region (UTR) of COX-2 mRNA. Synovial cells were transfected with agomiR-758-3p, and the MTT assay was performed to assess cell proliferation. The results demonstrated that COX-2 expression was higher in patients with KOA than those with acute knee trauma. Conversely, miR-758-3p expression was lower in patients with KOA than those with acute knee trauma. Notably, miR-758-3p interacted with the 3'-UTR of COX-2 mRNA to regulate its expression. Overexpression of miR-758-3p inhibited the expression and release of COX-2, as well as the proliferation of human KOA synovial cells. Taken together, these results suggest that COX-2 expression is upregulated in synovium tissues and synovial fluid from patients with KOA, which is associated with downregulated miR-758-3p expression. In addition, miR-758-3p affects the proliferation of synovial cells and the expression of relevant proteins in these cells, thus promoting the occurrence and development of KOA.

Long non-coding RNA X-inactive specific transcript promotes osteosarcoma metastasis via modulating microRNA-758/Rab16.

BACKGROUND: As a common malignant bone sarcoma, osteosarcoma (OS) affects the health and lives of many people. Here, we probed the effects of long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) and microRNA-758 (miR-758) on OS metastasis, and examined possible downstream effector. METHODS: Quantitative reverse transcription PCR (qRT-PCR) was performed to detect the expressions of XIST and miR-758 in OS tissues and cells. Cell transfection was carried out to alter the levels of XIST and miR-758 in OS cells, and cell viability, migration, and invasion were assessed. Subsequently, qRT-PCR and a dual-luciferase reporter assay were conducted to analyze the regulatory effects of XIST on miR-758 and miR-758 on Rab16. Finally, we investigated whether Rab16 was the downstream effector of XIST/miR-758 axis. RESULTS: XIST was highly expressed in OS tissues and cells, but the opposite was seen for miR-758. In OS cells, migration, invasion, and epithelial-mesenchymal transformation (EMT) was promoted by overexpression of XIST and miR-758 inhibitor, but were inhibited by XIST knockdown and miR-758 mimics. XIST regulated miR-758 expression, and miR-758 regulated Rab16 expression in OS cells. Overexpression of Rab16 reversed the effects of miR-758 mimics on OS cell migration and invasion. CONCLUSIONS: XIST contributed to OS cell migration, invasion, and EMT via regulation of miR-758/Rab16.

lncRNA CASC9 sponges miR­758­3p to promote proliferation and EMT in bladder cancer by upregulating TGF­ß2.

The long noncoding RNA cancer susceptibility candidate 9 (CASC9) has been revealed to be an oncogenic gene in several types of cancer, and high CASC9 expression is related to tumorigenesis and cancer progression. However, the role of CASC9 in bladder cancer (BC), particularly during epithelial­mesenchymal transition (EMT), has not been characterized. RT­qPCR, EdU, CCK­8, wound scratch, Transwell and flow cytometric assays were performed to detect CASC9 expression, miR­758­3p expression and their functions in BC. RNA FISH was used to detect CASC9 subcellular localization. Luciferase reporter assay, RT­qPCR assay and western blotting were used to explore the relationship of CASC9, miR­758­3p and TGF­ß2. In the present study, it was revealed that CASC9 regulated EMT in BC. CASC9 expression was significantly upregulated in BC cell lines and specimens compared to that in adjacent normal bladder tissues. Upregulated CASC9 was associated with increased invasion ability and poor prognosis of BC. CASC9 knockdown inhibited BC cell proliferation, migration and invasion. Furthermore, a bioinformatics study and luciferase reporter assays revealed that CASC9 functioned as a ceRNA for miR­758­3p. CASC9 inhibited microRNA (miR)­758­3p activity and resulted in the de­suppression of its target transforming growth factor (TGF)­ß2. TGF­ß signaling driven by TGF­ß2 was crucial for CASC9 to promote EMT in BC. Collectively, these results indicated that CASC9 sponged miR­758­3p to regulate the expression of TGF­ß2, which activated the TGF­ß signaling pathway and promoted proliferation and EMT in BC.

MicroRNA-758 inhibits cervical cancer cell proliferation and metastasis by targeting HMGB3 through the WNT/ß-catenin signaling pathway.

Cervical cancer (CC) remains a highly prevalent cancer and cause of mortality amongst women worldwide. miR-758 has been demonstrated to be associated with tumorigenesis by controlling the expression of oncogenic or tumor suppressor genes. However, the function and mechanisms of miR-758 in CC have not been well illustrated. The present study aimed to dissect the effect of miR-758 on the proliferation, migration and invasion of CC cells and determine the potential underlying molecular mechanism of these effects. qPCR results revealed that the expression of miR-758 was significantly decreased in CC tissues and cell lines compared with that in normal tissues and normal cells. Results of CCK-8, colony formation and Transwell assays revealed that miR-758 overexpression markedly decreased cell viability, proliferation, invasion and migration. However, miR-758 inhibitors significantly increased viability, proliferation, invasion and migration. In the mechanism study, we demonstrated that high mobility group box 3 (HMGB3) was a direct target of miR-758, and HMGB3 overexpression rescued the viability, proliferation, invasion and migration of HeLa cells reduced by an miR-758 mimic. It was demonstrated that HMGB3 regulated the WNT/ß-catenin signaling pathway under miR-758 regulation. In summary, these observations suggested that miR-758 is a tumor suppressor gene that can inhibit the metastatic phenotype of CC cells by negatively regulating HMGB3, which may present a path to novel therapeutic stratagems for CC therapy.

miR-758-3p suppresses human bladder cancer cell proliferation, migration and invasion by targeting NOTCH2.

MicroRNAs (miRs) are widely involved in regulating tumor development and progression. miR-758-3p has been reported to suppress the progression of various cancer types, including hepatocellular carcinoma. However, whether miR-758-3p has a role in bladder cancer (BC) has not been previously reported, and was thus investigated in the present study. It was revealed that miR-758-3p was downregulated in BC tissues and cell lines. Transfection with miR-758-3p mimics suppressed the proliferation, migration and invasion of BC cells, and inhibition of miR-758-3p had the opposite effect. In terms of the underlying mechanisms, a luciferase reporter assay revealed that Notch receptor 2 (NOTCH2) is a direct target gene of miR-758-3p in BC cells. Transfection with miR-758-3p mimics decreased the mRNA and protein levels of NOTCH2. Furthermore, an inverse correlation between miR-758-3p and NOTCH2 levels was identified. Finally, overexpression of NOTCH2 significantly rescued the proliferation, migration and invasion of BC cells transfected with miR-758-3p mimics. Taken together, the present study indicated that miR-758-3p suppresses BC cell proliferation, migration and invasion by targeting NOTCH2.

microRNA-758 inhibits the malignant phenotype of osteosarcoma cells by directly targeting HMGA1 and deactivating the Wnt/ß-catenin pathway.

microRNAs (miRNAs) are frequently aberrantly expressed in osteosarcoma (OS) and are implicated in its development. Dysregulation of miR-758 has been reported in various human malignancies. However, whether miR-758 is involved in the oncogenesis and progression of OS remains unclear. In this study, reverse transcription-quantitative polymerase chain reaction was performed to detect miR-758 expression in OS tissues and cell lines. A series of functional experiments were employed to explore the regulatory effects of miR-758 on the malignant behaviors of OS cells both in vitro and in vivo. The molecular mechanisms underlying the activity of miR-758 in OS cells were also investigated. miR-758 was significantly downregulated in OS tissues and cell lines, and a low miR-758 level was correlated with tumor size, clinical stage, and distant metastasis of patients with OS. OS patients with low miR-758 level exhibited poorer overall survival and worse disease-free survival rates compared to patients with high miR-758 level. In addition, functional assays revealed that miR-758 overexpression led to a significant decrease in OS cell growth and metastasis in vitro, whereas miR-758 inhibition had the opposite effect on OS cells. miR-758 reduced the tumorous growth of OS cells in vivo. Furthermore, high mobility group AT-hook 1 (HMGA1) was identified as a direct target of miR-758 in OS cells. HMGA1 was highly expressed in OS tissues, and its expression was inversely correlated with miR-758 expression. HMGA1 silencing exerted an effect similar to that induced by miR-758 upregulation in OS cells. Restored HMGA1 expression abolished the effects of miR-758 on the malignant phenotypes of OS cells. Moreover, miR-758 regulated the Wnt/ß-catenin pathway in OS cells in vitro and in vivo. To the best of our knowledge, this is the first study to demonstrate that miR-758 may inhibit the aggressive behavior of OS cells in vitro and in vivo by directly targeting HMGA1 and regulating the Wnt/ß-catenin pathway. These results will aid in elucidating the roles of miR-758 and suggest that the miR-758/HMGA1/Wnt/ß-catenin pathway represents a potential therapeutic target in OS.

Overexpression of miR-758 inhibited proliferation, migration, invasion, and promoted apoptosis of non-small cell lung cancer cells by negatively regulating HMGB.

Non-small cell lung cancer (NSCLC) is one of the most fatal types of cancer with significant mortality and morbidity worldwide. MicroRNAs (miRs) have been confirmed to have positive functions in NSCLC. In the present study, we try to explore the role of miR-758 in proliferation, migration, invasion, and apoptosis of NSCLC cells by regulating high-mobility group box (HMGB) 3 (HMGB3.) NSCLC and adjacent tissues were collected. Reverse transcription quantitative PCR (RT-qPCR) was employed to detect expression of miR-758 and HMGB3 in NSCLC and adjacent tissues, in BEAS-2B cells and NSCLC cell lines. The targetted relationship between miR-758 and HMGB3 was identified by dual luciferase reporter gene assay. The effects of miR-758 on proliferation, migration, invasion, cell cycle, and apoptosis of A549 cells. MiR-758 expression was lower in NSCLC tissues, which was opposite to HMGB3 expression. The results also demonstrated that miR-758 can target HMGB3. The cells transfected with miR-758 mimic had decreased HMGB3 expression, proliferation, migration, and invasion, with more arrested cells in G1 phase and increased apoptosis. Our results supported that the overexpression of miR-758 inhibits proliferation, migration, and invasion, and promotes apoptosis of NSCLC cells by negative regulating HMGB2. The present study may provide a novel target for NSCLC treatment.