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Purpose: The aim of this study was to reveal the biological function of endoplasmic reticulum stress (ERS)-related genes (ERSGs) in periodontitis, and provide potential ERS diagnostic markers for clinical therapy of periodontitis., Methods: The differentially expressed ERSGs (DE-ERSGs) were reveled based on periodontitis-related microarray dataset in Gene Expression Omnibus (GEO) database and 295 ERS in previous study, followed by a protein-protein interaction network construction. Then, the subtypes of periodontitis were explored, followed by validation with immune cell infiltration and gene set enrichment. Two machine learning algorithms were used to reveal potential ERS diagnostic markers of periodontitis. The diagnostic effect, target drug and immune correlation of these markers were further evaluated. Finally, a microRNA(miRNA)-gene interaction network was constructed., Results: A total of 34 DE-ERSGs were revealed between periodontitis samples and control, followed by two subtypes investigated. There was a significant difference of ERS score, immune infiltration and Hallmark enrichment between two subtypes. Then, totally 7 ERS diagnostic markers including FCGR2B, XBP1, EDEM2, ATP2A3, ERLEC1, HYOU1 and YOD1 were explored, and the v the time-dependent ROC analysis showed a reliable result. In addition, a drug-gene network was constructed with 4 up-regulated ERS diagnostic markers and 24 drugs. Finally, based on 32 interactions, 5 diagnostic markers and 20 miRNAs, a miRNA-target network was constructed., Conclusions: Up-regulated miR-671-5p might take part in the progression of periodontitis via stimulating the expression of ATP2A3. ERSGs including XBP1 and FCGR2B might be novel diagnostic marker for periodontitis., (© 2023. The Author(s).)

Background: Methamphetamine (MA) is an addictive psychostimulant substance that mainly leads to schizophrenia-like psychotic symptoms. The expression of miRNAs in brain plays an important role in neurological disorders and may affect by genetic variant(s) in the target site (MiRSNPs). In this study, we investigated whether polymorphisms in miRNAs are associated with MA disorder with psychosis., Methods: We carried out a case-control association study in 400 MA users with psychotic characters and 448 controls. Six MiRSNPs with predicted functional relevance miRNAs (miR-181b, miR-181a, miR-15b, miR-let-7e and miRlet-7d) were selected for genotyping. Allele and genotype frequencies were compared between MA users and healthy individuals. The expression of five miRNAs were measured by quantitative real-time RT-PCR in 55 cases and 57 controls. We also explored an expression Quantitative Trait Loci (eQTL) analysis based on the miRNAs expression and SNP genotype., Results: The SNP rs10760371 within miR-181a was nominally associated with MA disorder (P = 0.046). For rs1099308, rs10760371 and rs10993081 in strong linkage disequilibrium (LD), no significant association had been detected from haplotype analysis. Discrepancy had been found between MA users and healthy individuals (P < 0.01) in terms of the expression of miR-181a, miR-15b, miR-let-7e and miR-let-7d. and no noticeable difference had been found from the eQTL analysis., Conclusion: Our findings suggest that rs10760371 within miR-181a may relate to the development of MA dependence with psychosis. The miRNAs expression is unlikely to be regulated by the SNPs within it., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Recently, long noncoding RNAs (lncRNAs) are attracting wide attention in the field of cancer research because of its important role in cancer diagnosis and prognosis. But studies on the biological effects and relevant mechanisms of lncRNAs in non-small cell lung cancer (NSCLC) remain few and need to be enriched. Our study discussed the expression and biological effects of LncRNA NR2F2-AS1, and further explored its possible molecular mechanisms. As a result, elevated expression of NR2F2-AS1 was detected in NSCLC tissues and cells and was remarkably associated with the tumor, node, metastasis (TNM) stage and the status of lymphatic metastasis of patients. Down-regulated NR2F2-AS1 contributed to the promotion of cell apoptosis and the inhibition of cell proliferation and invasion in A549 and SPC-A-1 cells in vivo and vitro. Through bioinformatics analysis, NR2F2-AS1 functions as a ceRNA directly binding to miR-320b, BMI1 was a direct target of miR-320b. Combined with the following cellular experiments, the data showed that NR2F2-AS1 may influence the NSCLC cell proliferation, invasion and apoptosis through regulating miR-320b targeting BMI1., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Esophageal cancer is a common malignant tumor worldwide. Inherent and acquired drug resistance are the major challenges faced in anticancer chemotherapy. This study aimed to explore the effects of α-solanine in regards to the chemosensitivity of esophageal cancer cells. We found that α-solanine enhanced the sensitivity of EC9706 and KYSE30 cells to 5-flurouracil (5-FU) and cisplatin (Cis) by promoting drug-induced apoptosis. qRT-PCR and western blotting results showed that α-solanine treatment promoted miR-138 expression and decreased survivin expression in EC9706 and KYSE30 cells. α-solanine also enhanced the inhibitory effects of 5-Fu and Cis in EC9706 transplanted tumors in mouse models. Dual-Luciferase reporter assay results confirmed survivin as the direct target gene of miR-138. MiR-138 inhibited survivin expression in EC9706 and KYSE30 cells. And miR-138 mimic and si-survivin had similar effects with α-solanine in suppressing survivin expression and promoting cancer cell death. miR-138 inhibitor reversed the chemosensitivity-enhancing effect of α-solanine. In EC9706 and KYSE30 cells, survivin overexpression rescued the cancer cells from apoptosis caused by α-solanine and miR-138 mimic expression. From these findings, we conclude that α-solanine enhanced the chemosensitivity of esophageal cancer cells to chemotherapy via the miR-138/survivin pathway. This study provides insight into the molecular mechanism underlying the chemosensitivity-enhancing function of α-solanine and suggests a new chemotherapeutic strategy for esophageal cancer treatment.

MicroRNAs (miRNAs) are critical translational regulators that act as oncogenes or tumor-suppressor genes. qRT-PCR assay results showed that the expression levels of miR-125a-5p are lower in lung adenocarcinoma (AD) tissues than expression levels in adjacent non-neoplastic tissues. This relative expression was found to be significantly associated with lymph node metastases. Cell growth, apoptosis, caspase activity and Transwell invasion assay results showed that in two lung adenocarcinoma cell lines transfected with a miR-125a-5p mimic, proliferation and invasion rates were found to be significantly reduced, whereas the apoptosis rate of the miR-125a-5p mimic group was enhanced. Subsequent western blotting and luciferase reporter assays showed that miR-125a-5p is able to bind to putative binding sites within the mRNA 3' untranslated region (UTR) of neural precursor cell expressed, developmentally downregulated 9 (NEDD9). Our findings suggest that miR-125a-5p may serve as a therapeutic agent for lung adenocarcinoma through its major target, NEDD9.

In this work, the in vitro experiments about biological mechanisms of curcumin were conducted using the gastric cancer cell lines SGC-7901 and BGC-823. After 24-h exposure to curcumin at the concentrations of 5, 10, 15, 20, and 40 μmol/L, two cells showed the decreased proliferation and increased apoptosis abilities. Real-time PCR, Cell Counting Kit-8 (CCK-8) assay, western blotting, and cell apoptosis assay were used to further study the underlying mechanisms of curcumin. The first stage of our studies showed that curcumin affected the expression of miR-33b, which, in turn, affected the expression of the X-linked inhibitor of apoptosis protein (XIAP) messenger RNA (mRNA). Next, curcumin was also identified to regulate the proliferation and apoptosis of SGC-7901 and BGC-823 cells. Further bioinformatics analysis and luciferase reporter assays proved that XIAP was one of the target genes of miR-33b. In the next stage, SGC-7901 and BGC-823 cells were treated with 20 μL curcumin, miR-33b mimics, and small interfering RNA (siRNA) of XIAP, respectively. The results showed that curcumin had similar effects on cell growth and apoptosis as the upregulation of miR-33b and the upregulation of the siRNA of XIAP. The results that followed from the restore experiments showed that curcumin affected cell growth and apoptosis presumably by upregulating the XIAP targeting in gastric cancer. Collectively, our results indicate that curcumin-miR-33b-XIAP coupling might be an important mechanism by which curcumin induces the apoptosis of SGC-7901 and BGC-823 cells.

Recently, the incidence of melanoma has been on the rise. Patients with distant metastasis share poor prognosis. Increasing studies have been conducted to clarify the molecular mechanisms as well as to investigate potential effective therapeutic targets in the development of melanoma. This study focuses on the LncRNA UCA1 and its downstream regulated factors. In our experiments, UCA1 expression was discovered to be upregulated in melanoma tissues and cells, while the depletion of UCA1 led to the inhibition of cell proliferation, invasion and cell cycle arrest. To further our understanding of the mechanisms of UCA1, a system of experiments was built. We found that miR-507 could directly bind to UCA1 at the miRNA recognition site, and that there was a negative correlation between miR-507 and UCA1. Additionally, FOXM1 is a target of miR-507 and can be downregulated by either miR-507 overexpression or UCA1 depletion. Downregulated FOXM1 was analogous to the depletion of UCA1 and the overexpression of miR-507. These results, taken together, provide evidence for a novel UCA1 interaction regulatory network in tumorigenesis of melanoma.

Currently, lung cancer is still a main cause of malignancy-associated death worldwide. Even though various methods for prevention and treatment of lung cancer have been improved in recent decades, the 5-year survival rate has remained very low. Insights into the anticancer function of small-molecule anticancer compounds have opened our visual field about cancer therapy. α-Solanine has been well studied for its antitumor properties, but its effect in lung cancer and associated molecular mechanisms have not yet been evaluated. To explore the anticancer function of α-solanine, we performed an MTT assay, Transwell arrays, colony-forming survival assay, quantitative reverse transcription PCR (qRT-PCR), Western blotting, and dual luciferase reporter assays in A549 and H1299 cells. We found that α-solanine not only inhibited cell migration and invasion ability but also enhanced the chemosensitivity and radiosensitivity of A549 and H1299 cells. Moreover, we discovered that α-solanine could affect the expression of miR-138 and focal adhesion kinase (FAK), both of which were also found to affect the chemosensitivity and radiosensitivity of A549 and H1299 cells. In conclusion, α-solanine could affect miR-138 and FAK expression to restrict cell migration and invasion and enhance the chemosensitivity and radiosensitivity of A549 and H1299 cells. The α-solanine/miR-138/FAK cascade can probably be a potential therapy target against lung adenocarcinoma.

MiR-198 is involved in tumorigenesis, migration, invasion, and metastasis of various malignant cancers. However, the exact expression levels of miR-198 and the molecular mechanism underlying its role in lung adenocarcinoma require further exploration. In this study, quantitative real-time PCR was applied to study miR-198 and serine hydroxymethyltransferase 1 (SHMT1) expression in 47 paired lung adenocarcinoma tissues and adjacent nontumor lung tissues. Clinicopathological characters were analyzed. Pearson's correlation analysis was used to detect the relationship between miR-198 and SHMT1 expression. The function of miR-198 was explored by measuring cell proliferation, cell apoptosis, and the cell-cycle in vitro and in vivo. The target gene of miR-198 was certified using dual luciferase report assay. We found that in lung adenocarcinoma, miR-198 was significantly downregulated and SHMT1 was inversely upregulated. A strong negative correlation was noticed between miR-198 and SHMT1 expression. Further analysis revealed that miR-198 expression was associated with TNM stage and lymph node metastasis. Upregulated miR-198 could inhibit cell proliferation, enhance cell apoptosis, and lead to cell-cycle arrest in lung adenocarcinoma, which showed a more effective alteration than SHMT1 siRNA. Moreover, we identified SHMT1 as a target gene of miR-198. In conclusion, miR-198 suppressed proliferation of lung adenocarcinoma cells both in vitro and in vivo by directly targeting SHMT1. miR-198 may be a potential therapeutic target for lung adenocarcinoma in the near future.

Background: As the end product of the bacterial fermentation of dietary fiber in the colonic lumen, sodium butyrate (NaBt) has been reported to exert antitumor effects on colorectal cancer (CRC). In addition to functioning as a histone deacetylase (HDAC) inhibitor, NaBt also regulates the expression of microRNAs (miRNAs) to inhibit CRC cell proliferation. Yet, the mechanisms involved are not completely understood. Here we investigate whether NaBt regulates miR-203 to inhibit CRC growth and explore the promising target gene of miR-203 in CRC cells., Methods: We conducted qRT-PCR and Western blotting assays to evaluate the effects of NaBt on the expression of miR-203 and NEDD9 in HT-29 and Caco-2 cell lines. The promising target gene of miR-203 was predicted by miRNA target prediction and dual luciferase reporter assay. CRC Cell proliferation, colony formation, cell apoptosis and cell invasion assays were performed to explore the effect of NaBt, miR-203 and NEDD9 on HT-29 and Caco-2 cell lines., Results: The results showed that NaBt increased the expression of miR-203 to induce CRC cell apoptosis as well as inhibit cell proliferation, colony formation and cell invasion. Moreover, we determined that the NEDD9 was a target gene of miR-203. NEDD9 partially overcame the inhibitory effects of miR-203 on CRC cell colony formation and invasion., Conclusions: NaBt could induce CRC cell apoptosis, inhibit CRC cell proliferation, colony formation and invasion through miR-203/NEDD9 cascade. The present study may enrich the mechanisms underlying the process that NaBt exerts anti-tumor effects on CRC cells., (© 2016 S. Karger AG, Basel.)

Background: Esophageal cancer (EC) is one of the most common malignant tumors in the world. Due to difficulties with performing the operation, most patients choose to have palliative treatment instead. Radiotherapy is one of the main palliative treatments of EC. However, the clinical efficacy of radiotherapy is not satisfactory α-Solanine is a bioactive component of steroidal glycoalkaloids which has been demonstrated to exhibit anti-metastasis activity in different cancers. In the present study, we determined the effect of α-solanine on the radiosensitivity of EC cells and priliminarily explored the underlying molecular mechanisms., Methods: Cell Counting Kit-8 (CCK-8) assay was conducted to found the cytotoxic effect of α-solanine on EC cells. CCK-8 assay and colony-forming survival assays were performed to explore the effect of α-solanine on cell viability and proliferation of EC cells after irradiation. Immunofluorescence and comet assays were used to detect the effect of α-solanine on DNA repair capacity of EC cells after irradiation. The flow cytometry (FCM) and Hoechst/PI staining were conductd to study the effect of α-solanine on apoptosis of EC cells after irradiation., Results: The cytotoxic effect of α-solanine to EC cells was dose-dependent. The results of CCK-8, colony-forming survival assay, immunofluorescence, comet assay, FCM and Hoechst/PI staining showed that α-solanine could enhance the radiosensitivity of EC cells. α-Solanine could downregulate Survivin expression level by upregulating miR-138 expression in EC cells. Upregulation of miR-138 and knock down Survivin both enhanced the radiosensitivity of EC cells. Moreover, Survivin could restore the effect of α-solanine and miR-138 on radiosensitivity of EC cells., Conclusions: α-solanine could enhance the radiosensitivity of esophageal cancer cells by inducing microRNA-138 expression, and probably be an effective radiosensitizer in treating EC., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

Background: Aberrant expression of several types of miRNAs has been reported in acute myocardial infarction (AMI). The objective of our study was to compare miRNA expression in AMI patients and normal healthy people and determine whether miR-26a, miR-191, and miR-208b could be measured in plasma as indicators for AMI., Methods: Detection of AMI patients and normal persons by using miRNA microarray chip analysis and miR-26a, miR-191, and miR-208b was screened out. Eighty-seven AMI patients and eighty-seven homogeneous healthy individuals were recruited. Total mRNA including miRNA was isolated and miR-26a, miR-191, and miR-208b expression were determined by qRT-PCR. Receiver operating characteristic curve analysis was performed to evaluate the instructive power of miR-26a, miR-191, and miR-208b for AMI. Dual-luciferase reporter assays indicated p21 is a direct target of miR-208b., Results: miR-26a and miR-191 were low expressed in AMI compared with normal healthy people, but miR-208b was expressed at a high level in AMI. miR-26a showed an area under the curve (AUC) of 0.745, with a sensitivity of 73.6 % and a specificity of 72.4 %.The AUC for miR-191 was 0.669, with a sensitivity of 62.1 % and a specificity of 69.0 %.The AUC for miR-208b was 0.674, with a sensitivity of 59.8 % and a specificity of 73.6 %., Conclusions: miR-208b was significantly increased in the AMI compared with healthy people, while miR-26a and miR-191 were decreased. miR-26a, miR-191, and miR-208b were potential indices of AMI, and miR-208b was more effective in patients with non-ST-elevation myocardial infarction.

Background: Human DNA polymerase β (DNA polymerase β, polβ) is a small monomeric protein essential for short-patch base excision repair (BER). It plays an important role in regulating the sensitivity of tumor cells to chemotherapy., Methods: Luciferase reporter and western blot assays were used to determine whether polβ is a major target of miR-499. CCK-8, colony-forming survival and in vivo tumor growth assays were conducted to evaluate if miR- 499 can potentially enhance the cisplatin sensitivity and therefore inhibit the proliferation of esophageal cancer (EC) cells. Flow cytometry and immunofluorescence microscopy assays were performed to evaluate whether miR-499 enhance the cisplatin sensitivity and the corresponding apoptosis in EC cells., Results: polβ was pinpointed as a target gene of miR- 499. Additionally, we identified that miR-499 can enhance cisplatin's function of inhibiting proliferation and of promoting apoptosis in EC9706 and KYSE30 cell lines., Conclusions: We first investigated whether miR-499 modulates polβ, and observed the influence of miR-499 up-regulation on the sensitivity of EC cell lines to cisplatin treatment. Our study paves the way for more insightful understanding and application of chemotherapy in esophageal cancer in the future., (© 2015 S. Karger AG, Basel.)