Molecular medicine reports最新文献

Homeobox A5 (HOXA5) has been identified as a tumor suppressor gene in breast cancers, but its role in oral squamous cell carcinoma (OSCC) has not been confirmed. The Illumina GoldenGate Assay for methylation identified that DNA methylation patterns differ between tumorous and normal tissues in the oral cavity and that HOXA5 is one of the genes that are hypermethylated in oral tumor tissues. The present study obtained more‑complete information on the methylation status of HOXA5 by using the Illumina Infinium MethylationEPIC BeadChip and bisulfite sequencing assays. The results indicated that HOXA5 hypermethylation has great potential as a biomarker for detecting OSCC. Comparing HOXA5 RNA expression between normal oral tissue and OSCC tissue samples indicated that its median level was 2.06‑fold higher in normal tissues that in OSCC tissues. Moreover, treatment using the demethylating agent 5‑aza‑2'‑deoxycytidine can upregulate HOXA5 expression in OSCC cell lines, verifying that the silencing of HOXA5 is primarily regulated by its hypermethylation. It was also found that upregulation of HOXA5 expression can not only increase OSCC cell death but that it can also enhance the therapeutic effect of cisplatin both in vitro and in vivo, suggesting that HOXA5 is an epigenetically downregulated proapoptotic gene in OSCC.

Peptidyl‑prolyl cis‑trans isomerase NIMA-interacting 1 (Pin1) is a specific phosphorylated serine/threonine-proline cis-trans isomerase, which is involved in the regulation of a variety of physiological and pathological processes, including cell cycle progression, proliferation and apoptosis. Pin1 plays a key role in tumorigenesis and tumor development and it promotes the proliferation and metastasis of cancer cells by regulating the cell cycle, signaling pathways and the function of tumor suppressors. Upregulated expression of Pin1 is closely associated with a poor prognosis in several types of cancers. Thus, Pin1 is may have potential as a novel potential biomarker for tumor diagnosis and prognosis, as well as a promising anticancer target. The aim of the present review was to discuss the mechanism of Pin1 in tumors and recent research progress in this field.

Following the publication of the above paper, a concerned reader drew to the attention of the Editorial Office that the 'Sham' brain image featured in Fig. 1B on p. 23 was strikingly similar to an image that was published subsequently in the journal Scientific Reports, whereas the control TUNEL assay data shown in Fig. 4A on p. 25 were similarly strikingly similar to data shown in a paper published previously in the journal Mediators of Inflammation, even though the overall experiments portrayed in the other journals were different. As the three affected articles did hold at least one author in common, we asked the authors to provide an explanation to account for the sharing of these data among these papers, but no reply was forthcoming from them; therefore, in the absence of a reply from these authors, the Editor of Molecular Medicine Reports has decided that this paper should be retracted from the Journal on account of a lack of confidence in the presented data. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 17: 21‑30, 2018; DOI: 10.3892/mmr.2017.7858].

Rotator cuff tears (RCT) can cause shoulder pain, weakness and stiffness, significantly affecting daily life. Analysis of the GSE103266 dataset revealed significant changes in the mTOR/PI3K/Akt signaling pathway and lipid metabolism‑related pathways, suggesting that fatty infiltration may affect RCT. The analysis indicated that the ubiquitin ligase NEDD4 plays a critical role in RCT. NEDD4 was found to be highly associated with the mTOR/PI3K/Akt signaling pathway. An RCT model in Sprague‑Dawley (SD) rats was established to study the role of NEDD4 in regulating the mTOR pathway and investigate its effects on fatty infiltration. SD rats were divided into NEDD4 overexpression and knockout groups. Tissue recovery, apoptosis and fat deposition were measured through histological staining, reverse transcription‑quantitative PCR and western blotting. Additionally, cell culture of fibro‑adipogenic progenitors and lentiviral transfection were conducted to investigate the effect of NEDD4 on adipocyte differentiation. NEDD4 overexpression significantly reduced lipid accumulation, whereas NEDD4 knockdown enhanced lipid accumulation. NEDD4 was found to regulate the mTOR pathway and the expression of adipogenesis‑related genes, promoting fat metabolism and inhibiting adipocyte differentiation. Histological analysis indicated that NEDD4 overexpression improved tissue recovery and reduced apoptosis. Targeting NEDD4 offers a potential therapeutic strategy to improve the clinical outcomes of patients with RCT by modulating the mTOR pathway and fat metabolism.

Calycosin‑7‑O‑β‑D‑glucoside (CG), a major active ingredient of Astragali Radix, exerts neuroprotective effects against cerebral ischemia; however, whether the effects of CG are associated with mitochondrial protection remains unclear. The present study explored the role of CG in improving mitochondrial function in a HT22 cell model of oxygen‑glucose deprivation/reperfusion (OGD/R). The Cell Counting Kit‑8 assay, flow cytometry, immunofluorescence and western blotting were performed to investigate the effects of CG on mitochondrial function. The results demonstrated that mitochondrial function was restored after treatment with CG, as indicated by reduced mitochondrial reactive oxygen species levels, increased mitochondrial membrane potential and improved mitochondrial morphology. Overactivated mitophagy was revealed to be inhibited by the regulation of proteins involved in fission [phosphorylated‑dynamin‑related protein 1 (Drp1) and Drp1] and mitophagy (LC3, p62 and translocase of outer mitochondrial membrane 20), and mitochondrial biogenesis was demonstrated to be enhanced by increased levels of sirtuin 1 (SIRT1) and peroxisome proliferator‑activated receptor γ coactivator‑1α (PGC‑1α). In addition, neuronal apoptosis was ameliorated by CG, as determined by a decreased rate of apoptosis, and levels of caspase‑3 and Bcl‑2/Bax. In conclusion, the present study demonstrated that CG may alleviate OGD/R‑induced injury by upregulating SIRT1 and PGC‑1α protein expression, and reducing excessive mitochondrial fission and overactivation of mitophagy.

Asiasarum root and rhizome (Asarum) is commonly used as a diaphoretic. Due to its warm and pungent characteristics in traditional Chinese and Korean medicine, it is considered as having the potential to prevent disease. The present study investigated the effects of Asarum extract on the symptoms of obesity in mice, and the regulation of energy metabolism in the liver and skeletal muscle tissues. In addition, to identify the potential molecular targets and signaling pathways involved in the mechanism of action of Asarum extract in obesity, network pharmacological and molecular docking analysis was performed. In vitro studies demonstrated that Asarum extract significantly increased the expression of regulators of energy metabolism [sirtuin 1 (SIRT1), peroxisome proliferator‑activated receptor γ coactivator 1‑α (PGC1α), nuclear respiratory factor 1, AMP‑activated protein kinase (AMPK) and glucose transporter type 4 (GLUT4)] and myogenic regulatory factors (MyoD, myogenin and myosin heavy chain) in C2C12 myotubes. Furthermore, the in vivo studies demonstrated that Asarum extract could reduce increases in body weight, and the levels of blood glucose, insulin, total cholesterol, triglycerides and low‑density lipoprotein cholesterol in the sera of obese mice. Asarum extract also improved pathological changes in the liver and pancreatic tissues of obese mice, and significantly increased the ratio of brown fat mass to body weight. In addition, Asarum extract reversed the expression of energy metabolism regulators and myogenic regulatory factors in the gastrocnemius tissues of obese mice. Asarum extract also activated the expression of SIRT1, PGC1α and AMPK in the liver tissues of obese mice. These findings indicated that Asarum extract may exert anti‑obesity effects, such as body weight loss, decreases in lipid metabolite levels, and inhibition of pancreatic and liver damage. Using network pharmacological analysis, the mechanisms underlying the effects of Asarum extract on the regulation of energy metabolism were explored, particularly in skeletal muscle and liver tissues.

Small heat shock proteins (sHSPs) are common molecular chaperone proteins that function in various biological processes, and serve indispensable roles in maintaining cellular protein homeostasis and regulating the hydrolysis of unfolded proteins. HSP22 is a member of the sHSP family that is primarily expressed in the heart and skeletal muscle, as well as in various types of cancer. There have been important findings concerning the role of HSP22 in cardiovascular diseases. The aim of the present study was to provide insights into the various molecular mechanisms by which HSP22 functions in the heart, including oxidative stress, autophagy, apoptosis, the subcellular distribution of proteins and the promoting effect of proteasomes. In addition, drugs and cytokines, including geranylgeranylacetone, can exert protective effects on the heart by regulating the expression of HSP22. Based on increasingly abundant research, HSP22 may be considered a potential therapeutic target in cardiovascular diseases.

Hepatocellular carcinoma (HCC) is a common cause of cancer‑related mortality and morbidity worldwide. While iodine‑125 (¹²⁵I) particle brachytherapy has been extensively used in the clinical treatment of various types of cancer, the precise mechanism underlying its effectiveness in treating HCC remains unclear. In the present study, MHCC‑97H cells were treated with ¹²⁵I, after which, cell viability and proliferation were assessed using Cell Counting Kit‑8, 5‑ethynyl‑2'‑deoxyuridine and colony formation assays, cell invasion and migration were evaluated using wound healing and Transwell assays, and cell apoptosis was determined using flow cytometry. Omics data were analyzed using Kyoto Encyclopedia of Genes and Genomes, Gene Ontology and STRING analyses to observe the key genes that exhibited significant changes at the transcriptional and protein levels in MHCC‑97H cells treated with ¹²⁵I particles. Finally, the expression levels of key genes (GPNMB, C4BPA, CTH, H1‑0 and MT2A) were verified through reverse transcription quantitative PCR. Following treatment with ¹²⁵I, the proliferation, invasion and migration of MHCC‑97H cells were inhibited, and apoptosis was enhanced. The results of omics data analysis indicated that the biological behavior of MHCC‑97H cells treated with ¹²⁵I was related to the expression levels of CTH and MT2A genes. These findings indicated that intervention with ¹²⁵I radiation particles may induce changes in gene expression, potentially influencing alterations in biological characteristics. In conclusion, these insights may shed light on the underlying mechanisms of ¹²⁵I radiation particle therapy in HCC and offer novel targets for HCC treatment.

Insulin‑like growth factor 2 mRNA binding protein 2 (IGF2BP2) is an RNA binding protein that functions as an N⁶‑methyladenosine reader. It regulates various biological processes in human cancers by affecting the stability and expression of target RNA transcripts, including coding RNAs and non‑coding RNAs (ncRNAs). Numerous studies have shown that IGF2BP2 expression is aberrantly increased in various types of cancer and plays multifaceted roles in the development and progression of human cancers. In the present review, the clinical importance of IGF2BP2 is summarized and its involvement in the regulation of biological processes, including proliferation, metastasis, chemoresistance, metabolism, tumor immunity, stemness and cell death, in human cancers is discussed. The chemical compounds that have been developed as IGF2BP2 inhibitors are also detailed. As ncRNAs are now important potential therapeutic agents for cancer treatment, the microRNAs that have been reported to directly target and inhibit IGF2BP2 expression in cancers are also described. In summary, by reviewing the latest literature, the present study aimed to highlight the clinical importance and physiological functions of IGF2BP2 in human cancer, with a focus on the great potential of IGF2BP2 as a target for inhibitor development. The present review may inspire new ideas for future studies on IGF2BP2, which may serve as a specific therapeutic target in cancer.

Cartilage‑hair hypoplasia (CHH) is an autosomal recessive form of metaphyseal chondrodysplasia caused by RNA component of mitochondrial RNA processing endoribonuclease (RMRP) gene variants; however, its molecular etiology remains unclear. Whole‑exome sequencing was performed to detect possible pathogenic variants in a patient with a typical short stature and sparse hair. A co‑segregation analysis was also conducted and variants in the family members of the patient were confirmed by Sanger sequencing. A novel compound heterozygous variant in RMRP (NR_003051.4: n.‑21_‑2dup and n.197C>T) was identified in the affected patient. Data from 2 years and 4 months of follow‑up showed a positive effect of growth hormone (GH) therapy on height. Subsequently, two gene expression profiles associated with CHH were obtained from the EMBL‑EBI ENA and ArrayExpress databases. Differentially expressed genes between patients with CHH and healthy controls were selected using R software and were subjected to core analysis using ingenuity pathway analysis (IPA) software. IPA core analysis showed that the 'cell cycle checkpoints' was the most prominent canonical pathway, and the top enriched diseases and functions included various types of cancer, immunological diseases, development disorders and respiratory diseases. The integrative analysis displayed that RMRP can regulate the aberrant expression of downstream targets mainly via the transcription factor TP53, which results in the inhibition of 'cell cycle checkpoints'; eventually, functions associated with the CHH phenotype, such as 'growth failure or short stature' are activated. In conclusion, novel disease‑causing genetic variants of RMRP expand the genetic etiology of CHH, which must be clinically differentiated from achondroplasia. The findings of the present study provide new insights into the mechanisms underlying CHH.