Circ_RPPH1 facilitates progression of breast cancer via miR-1296-5p/TRIM14 axis.

Circular RNA Ribonuclease P RNA Component H1 (circ_RPPH1) and microRNA (miRNA) miR-1296-5p play a crucial role in breast cancer (BC), but the molecular mechanism is vague. Evidence showed that miR-1296-5p can activate tripartite motif-containing 14 (TRIM14). Clinical indications of eighty BC patients were collected and the circ_RPPH1 expression was detected using real-time quantitative PCR. MCF-7 and MDA-MB-231 cells were transfected with overexpression or knockdown of circ_RPPH1, miR-1296-5p, or TRIM14. Cell counting kit-8, cell cloning formation, wound healing, Transwell, and flow cytometry assays were performed to investigate the malignant phenotype of BC. The dual-luciferase reporter gene analyses were applied to reveal the interaction between these target genes. Subcutaneous tumorigenic model mice were established with circ_RPPH1 overexpression MDA-MB-231 cells in vivo; the tumor weight and volume, levels of miR-1296-5 and TRIM14 mRNA were measured. Western blot and immunohistochemistry were used to detect TRIM14 in cells and mice. Circ_RPPH1 levels were notably higher in BC patients and have been found to promote cell proliferation, invasion, and migration of BC cells. Circ_RPPH1 altered cell cycle and hindered apoptosis. Circ_RPPH1 knockdown or miR-1296-5p overexpression inhibited the malignant phenotype of BC. Furthermore, miR-1296-5p knockdown reversed circ_RPPH1's promotion effects on BC. Interestingly, TRIM14 overexpression counteracts the inhibitory effects of miR-1296-5p overexpression and circ_RPPH1 silencing on BC. Moreover, in BC tumor-bearing mice, circ_RPPH1 overexpression led to increased TRIM14 expression and facilitated tumor growth. Circ_RPPH1 enhanced BC progression through miR-1296-5p/TRIM14 axis, indicating its potential as a biomarker and therapeutic target in BC.

Tripartite motif­containing 14 may aggravate cardiac hypertrophy via the AKT signalling pathway in neonatal rat cardiomyocytes and transgenic mice.

Tripartite motif­containing 14 (TRIM14) is an E3 ubiquitin ligase that primarily participates in the natural immune response and in tumour development via ubiquitination. However, the role of TRIM14 in cardiac hypertrophy is not currently clear. The present study examined the role of TRIM14 in cardiac hypertrophy and its potential molecular mechanism. TRIM14 was overexpressed in neonatal rat cardiomyocytes using adenovirus and cardiomyocyte hypertrophy was induced using phenylephrine (PE). Cardiomyocyte hypertrophy was assessed by measuring cardiomyocyte surface area and markers of hypertrophy. In addition, TRIM14­transgenic (TRIM14­TG) mice were created and cardiac hypertrophy was induced using transverse aortic constriction (TAC). Cardiac function, heart weight­to­body weight ratio (HW/BW), cardiomyocyte cross­sectional area, cardiac fibrosis and hypertrophic markers were further examined. The expression of AKT signalling pathway­related proteins was detected. TRIM14 overexpression in cardiomyocytes promoted PE­induced increases in cardiomyocyte surface area and hypertrophic markers. TRIM14­TG mice developed worse cardiac function, greater HW/BW, cross­sectional area and cardiac fibrosis, and higher levels of hypertrophic markers in response to TAC. TRIM14 overexpression also increased the phosphorylation levels of AKT, GSK­3ß, mTOR and p70S6K in vivo and in vitro. To the best our knowledge, the present study was the first to reveal that overexpression of TRIM14 aggravated cardiac hypertrophy in vivo and in vitro, which may be related to activation of the AKT signalling pathway.

[Retracted] Tripartite motif­containing 14 regulates cell proliferation and apoptosis in cervical cancer via the Akt signaling pathway.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the GAPDH control western blotting data shown in Fig. 2B were strikingly similar to data appearing in different form in Fig. 1E in another article written by different authors at different research institutes [Liang T, Ye X, Liu Y, Qiu X, Li Z, Tian B and Yan D: FAM46B inhibits cell proliferation and cell cycle progression in prostate cancer through ubiquitination of ß­catenin. Exp Mol Med 50: 1­12, 2018]. 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. 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. [Molecular Medicine Reports 22: 5145­5154, 2020; DOI: 10.3892/mmr.2020.11634].

Long non-coding RNA OIP5-AS1 contributes to cisplatin resistance of oral squamous cell carcinoma through the miR-27b-3p/TRIM14 axis.

Oral squamous cell carcinoma (OSCC) accounts for 90% of oral cavity cancer types, but the overall prognosis for patients with OSCC remains unfavorable. Cisplatin (DDP) is an effective drug in OSCC treatment, but DDP resistance weakens its therapeutic effect. Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) can trigger DDP resistance. The purpose of the current study was to explore the role and mechanism ofOIP5-AS1 in OSCC DDP resistance. In the present study, the expression levels of OIP5-AS1, microRNA (miR)-27b-3p and tripartite motif-containing 14 (TRIM14) were detected by reverse transcription-quantitative PCR. DDP resistance was measured using an MTT assay. Moreover, cell proliferation, migration and invasion were assessed by MTT, Transwell, and Matrigel assays. Protein expression levels of TRIM14, E-cadherin, N-cadherin and Vimentin were detected by western blot analysis. Putative binding sites between miR-27b-3p andOIP5-AS1 or TRIM14werepredicted with starBase and verified using a dual-luciferase reporter assay. The role of OIP5-AS1 in DDP resistance of OSCC in vivo was measured using a xenograft tumor model. It was observed that OIP5-AS1 was upregulated in DDP-resistant OSCC cells, and the knockdown of OIP5-AS1 improved DDP sensitivity in DDP-resistant OSCC cells. The present study identified that miR-27b-3p was a target of OIP5-AS1. Furthermore, miR-27b-3p silencing reversed the effect of OIP5-AS1 knockdown on DDP sensitivity in DDP-resistant OSCC cells. TRIM14was shown to be a direct target of miR-27b-3p, and TRIM14 overexpression abolished the effect of miR-27b-3p on DDP sensitivity in DDP-resistant OSCC cells. The results suggested that OIP5-AS1 increased TRIM14 expression by sponging miR-27b-3p. In addition, OIP5-AS1 knockdown enhanced DDP sensitivity of OSCC in vivo. Data from the present study indicated that OIP5-AS1 may improve DDP resistance through theupregulationTRIM14 mediated bymiR-27b-3p, providing a possible therapeutic strategy for OSCC treatment.

Disturbed Yin-Yang balance: stress increases the susceptibility to primary and recurrent infections of herpes simplex virus type 1.

Herpes simplex virus type 1 (HSV-1), a neurotropic herpes virus, is able to establish a lifelong latent infection in the human host. Following primary replication in mucosal epithelial cells, the virus can enter sensory neurons innervating peripheral tissues via nerve termini. The viral genome is then transported to the nucleus where it can be maintained without producing infectious progeny, and thus latency is established in the cell. Yin-Yang balance is an essential concept in traditional Chinese medicine (TCM) theory. Yin represents stable and inhibitory factors, and Yang represents the active and aggressive factors. When the organism is exposed to stress, especially psychological stress caused by emotional stimulation, the Yin-Yang balance is disturbed and the virus can re-engage in productive replication, resulting in recurrent diseases. Therefore, a better understanding of the stress-induced susceptibility to HSV-1 primary infection and reactivation is needed and will provide helpful insights into the effective control and treatment of HSV-1. Here we reviewed the recent advances in the studies of HSV-1 susceptibility, latency and reactivation. We included mechanisms involved in primary infection and the regulation of latency and described how stress-induced changes increase the susceptibility to primary and recurrent infections.

High Levels of TRIM14 Are Associated with Poor Prognosis in Hepatocellular Carcinoma.

BACKGROUND: Tripartite motif containing 14 (TRIM14) has been reported to play a critical role in tumor development. However, little is known about TRIM14 expression and its clinical significance in hepatocellular carcinoma (HCC). The aim of the present study was to investigate the expression and prognostic value of TRIM14 in patients with HCC. MATERIALS AND METHODS: The mRNA and protein levels of TRIM14 in HCC were evaluated by quantitative real-time polymerase chain reaction, Western blot analysis, and immunohistochemistry. The association of TRIM14 expression with clinicopathological factors, overall survival (OS), and recurrence-free survival (RFS) was analyzed. RESULTS: TRIM14 expression was significantly upregulated in HCC-related tissues. High TRIM14 expression correlated with C-reactive protein (p = 0.01), alanine aminotransferase (p = 0.02), tumor size (p = 0.005), lesion number (p = 0.023), vascular invasion (p = 0.041), tumor/node/metastasis (TNM) stage (p = 0.001), and Barcelona Clinic Liver Cancer (BCLC) stage (p = 0.003). In addition, high TRIM14 expression was associated with poor OS and RFS (both p < 0.001). Cox regression analysis revealed that high TRIM14 expression was an independent prognostic factor for both OS (hazard ratio (HR) 1.657, 95% confidence interval (CI) 1.031-2.687; p = 0.018) and RFS (HR 2.297, 95% CI 1.184-2.312; p = 0.007). CONCLUSION: TRIM14 is a potential prognostic predictor for OS and RFS in patients with HCC.

Target therapy of TRIM-14 inhibits osteosarcoma aggressiveness through the nuclear factor-κB signaling pathway.

Osteosarcoma is the most common cause of cancer-associated mortality and the prognosis is yet to be fully elucidated due to the paucity of effective therapeutic targets that significantly influence the quality of life and mean survival rates of patients with osteosarcoma. Studies have showed that tripartite motif-containing (TRIM)-14 is a member of the TRIM protein family that has a vital role in tumor progression and metastasis and promotes angiogenesis, invasion and apoptotic resistance of bone cancer. In this study, a chimeric antibody targeting TRIM-14 (Chanti-TRIM) was constructed and the molecular mechanism of target therapy for TRIM-14 was investigated in osteosarcoma cells and xenograft mice. The growth, migration and invasion properties of U-2OS cells were analyzed following incubation with 10-160 mg/ml Chanti-TRIM. Apoptosis of U-2OS cells was detected after Chanti-TRIM treatment. Matrix metalloproteinase (MMP)-9-mediated nuclear factor-κB (NF-κB) signal pathway was analyzed in U-2OS cells treated with Chanti-TRIM. The inhibitory efficacy of Chanti-TRIM was studied in U-2OS-bearing xenograft mice. Our results demonstrated that neutralizing TRIM-14 expression markedly inhibited the growth, migration and invasion of osteosarcoma cells, in vitro and in vivo. We found that TRIM-14 depletion decreased cell viability and induced cells apoptosis in vitro. In addition, we identified Chanti-TRIM inhibited growth and promoted apoptosis induced by cisplatin through MMP-9-mediated NF-κB signal pathway. Furthermore, we observed that Chanti-TRIM treatment inhibited osteosarcoma growth in vivo. Histological analysis indicated that apoptotic bodies were increased and NF-κB nuclear translocation factors, including Ikkß, p65 and IkBα, were decreased in tumors treated by Chanti-TRIM. In conclusion, these results showed that Chanti-TRIM markedly inhibited the progression of osteosarcoma, suggesting Chanti-TRIM may be a potential anti-cancer agent that functions via the activation of the NF-κB pathway for osteosarcoma.