Critical Reviews in Eukaryotic Gene Expression最新文献

The cancer-promoting function of the long non-coding RNA (lncRNA) LPP-AS2 has been documented in different cancers. Nonetheless, its role in thyroid carcinoma (THCA) remains unestablished. Reverse transcription quantitative polymerase chain reaction and Western blotting were conducted to estimate the expressions of lncRNA LPP-AS2, miR-132-3p, and OLFM1. The THCA cells' functions were assessed through CCK8 assays, Transwell invasion assays, scratch wound-healing migration assays, and quantification of caspase-3 activity. The in vivo assays were also implemented to assess tumor growth. Luciferase reporter and RNA immuno-precipitation assay (RIPA) experiments were executed to elucidate the interactions of miR-132-3p with lncRNA LPP-AS2 and OLFM1. THCA tissues and cells exhibited poor lncRNA LPP-AS2 and OLFM1 expressions and a robust expression of miR-132-3p. Overexpressing lncRNA LPP-AS2 constrained THCA cell proliferation, migration, and invasion and improved caspase-3 activity. The anti-tumor function of lncRNA LPP-AS2 was also validated in vivo. miR-132-3p had an interplay with lncRNA LPP-AS2 and OLFM1. Functionally, overexpressing miR-132-3p promoted the malignant THCA cell phenotypes. However, that tumor promotion was abolished by the additional overexpression of lncRNA LPP-AS2. The in vitro experiments also demonstrated that the repressive effect of OLFM1 overexpression on THCA cell malignant action could be offset by the miR-132-3p mimic. lncRNA LPP-AS2 impedes THCA progression via the miR-132-3p/OLFM1 axis. Our findings contribute a potential strategy in interfering with THCA progression.

Background: The importance of BAG2 in malignancy is gradually being recognized, however, information on its role in uveal melanoma (UVM) is limited. We aimed to elucidate its function and potential mechanism of action in UVM.

Methods: Using the Cancer Genome Atlas (TCGA) and GEO-related datasets, we analyzed the differential expression of BAG2 in tumors, combined with clinical information and methylation data to analyze the prognostic value of BAG2, differential methylation and its association with UVM metastasis. In addition, correlation analysis explored the immunological characteristics of BAG2 in UVM and the response to immunotherapy. Finally, a prognostic model of ferroptosis- related genes was constructed and validated.

Results: BAG2 is significantly downregulated in multiple cancers including UVM. Prognostic analysis showed that BAG2 was an independent prognostic factor for UVM. Abnormal methylation of BAG2 may affect the metastasis of UVM and be significantly associated with poor prognosis. Immune analysis clarified that BAG2 was significantly associated with UVM immune cell infiltration and multiple immune checkpoints, and low expression of BAG2 was more beneficial in immunotherapy. In addition, the prognostic model of ferroptosis we constructed has good performance in predicting overall survival and metastasis-free survival of UVM.

Conclusions: BAG2 is an independent prognostic factor for UVM and may be a potential immune checkpoint for UVM.

The malignant bone tumor osteosarcoma (OS) was one of the most aggressive tumors. Despite breakthroughs in treatment options for OS recently, the survival rate of patients with metastasis or reoccurring disease has remained unchanged over the last 25 years, at around 20%. lncRNA expression dysregulation is linked to carcinogenesis, advancement, and metastasis. Additionally, the fundamental mechanism of lncRNAs in regulating OS cell biological activity and progression is still being investigated. The expression of miR-873-5p and MALAT1 were detected by quantitative real-time polymerase chain reaction (qRT-PCR) in OS. The relationship between the expression level of MALAT1 and the survival rate of OS individuals was evaluated by the Kaplan-Meier plotter. The tumor cell's capability of proliferation was determined using the CCK-8. Transwell was used to test the migratory and invasive properties of tumor cells. ROCK1 protein expression was analyzed by western blot, while qRT-PCR was used to detect ROCK1 mRNA expression. Targeted genes of MALAT1 or miR-873-5p were predicted by StarBase2.0. The target association among miR-873-5p and MALAT1 or ROCK1 was confirmed using the luciferase assay. The relationship between ROCK1 and MALAT1 or miR-873-5p expression in OS was investigated using Spearman's correlation analysis. MALAT1 was up-regulated and was linked to a lower survival rate of patients in OS. The malignant behaviors of cells were inhibited by down-regulated MALAT1 in vitro. Dual-luciferase gene experiments confirmed the presence of MALAT1/miR-873-5p/ROCK1 axis. The up-regulated miR-873-5p blocked the promoted effects of MALAT1 on cell behaviors. Over-expressed MALAT1 promoted the malignant behaviors of cells by miR-873-5p/ROCK1 axis in OS.

Tumor angiogenesis is considered to be an important part of the mechanism of tumor progression and metastasis, and its specific function in lung adenocarcinoma has not been fully studied. In this study, we used the transcriptome and genome data of lung adenocarcinoma patients to analyze the expression of 36 angiogenesis regulators in lung adenocarcinoma. Consensus clustering analysis divided lung adenocarcinoma samples into 4 subtypes, A, B, C, and D, and the expression of most angiogenesis regulators in subtype B was higher than that in other subtypes. Immunological analysis indicated that subtype B is likely to display the characteristics of a hot tumor with a more active TME. With the help of Lasso-Cox regression analysis, we successfully constructed a risk model involving five Angiogenesis Regulators genes (CCND2, JAG1, MSX1, STC1, TIMP1), which will be helpful for clinical personalized treatment and prognosis prediction. In addition, JAG1 has the highest mutation rate in tumors, and its cancer-promoting function is reflected in a variety of tumors, which provides important clues for the development of new broad-spectrum anti-cancer targets in the future. We successfully constructed a risk model involving five angiogenesis regulators genes (CCND2, JAG1, MSX1, STC1, TIMP1), which may be helpful for clinical personalized treatment and prognosis prediction. In addition, JAG1 has the highest mutation rate in tumors and plays a leading role in the protein interaction network. Its tumor-promoting function is reflected in a variety of tumors and may become a broad-spectrum anti-cancer target in the future.

The human papillomavirus is associated with a range of cancers. A vaccine introduced in 2006 has dramatically decreased the incidence of these cancers, but Americans still experience over 47,000 new cases of HPV-related cancers each year. The situation is worse in rural areas, where vaccination rates lag the national average, making HPV a significant health disparity issue. This article lays out an evidence-based HPV vaccine-promotion strategy that will serve as part of a campaign to improve health equity in rural northern New England in a process that is repeatable and sustainable. The campaign includes the following elements: partnerships with state departments of health and trusted community opinion leaders, evidence-based storytelling, local social media, traditional media, and school-based pop-up vaccination clinics. Borrowing from marketing and social marketing frameworks and guided by public health perspectives, we begin with psychographic and geodemographic information about our target audience, followed by a discussion about relevant models, frameworks, and research related to persuasive storytelling. We conclude with the outline of a guidebook to foster the creation of persuasive stories as part of a sustainable, replicable HPV vaccination campaign.

Long non-coding RNA LMCD1 antisense RNA 1 (LMCD1-AS1) has recently been reported to participate in the pathogenesis of several tumors, including thyroid cancer and osteosarcoma. However, the clinical significance of LMCD1-AS1 and the related biological function have not been reported in cervical cancer (CC). In this study, we observed that LMCD1-AS1 expression was highly expressed in CC specimens compared with adjacent normal specimens using quantitative real-time PCR. Chi-square test showed that high LMCD1-AS1 expression was correlated with FIGO stage and lymph node metastasis. Kaplan-Meier survival analysis showed poor prognosis with high LMCD1-AS1 expression. Moreover, FIGO stage, lymph node metastasis and high LMCD1-AS1 expression could be independent prognostic factors for the patients with CC. Functionally, knockdown of LMCD1-AS1 suppressed the proliferation, migration and invasion of two CC cell lines (HeLa and CaSki) cells by CCK-8 assay, colony formation assay, and Transwell assay. Knockdown of LMCD1-AS1 upregulated E-cadherin expression and downregulated the expression of PCNA, N-cadherin, and imentin in HeLa and CaSki cells. Luciferase reporter assay and RIP assay were conducted to evaluate the downstream molecular mechanisms of LMCD1-AS1. LMCD1-AS1 possesses a putative miR-873-3p-binding site and confirmed the negative correlation between them in CC tissues. Moreover, overexpression of LMCD1-AS1 promoted CC cell proliferation and EMT process through the regulation of miR-873-3p. In addition, depletion of LMCD1-AS1 reduced tumor growth and Ki-67 protein expression. In summary, our findings indicate that LMCD1-AS1 might exert an oncogenic role in CC and targeting LMCD1-AS1 might be a promising therapeutic target for CC treatment.

This study is aimed to investigate the clinical significance and biological function of long non-coding RNA somatostatin receptor 5 antisense RNA 1 (SSTR5-AS1) in prostate cancer (PCa). Here, we found that SSTR5-AS1 expression was upregulated in PCa tissues compared with adjacent tissues using quantitative real time PCR analysis. The results from Chi-square test showed that increased SSTR5-AS1 expression levels were correlated with preoperative prostate specific antigen, tumor stage and lymph node metastasis. Kaplan-Meier survival curve described patients with high SSTR5-AS1 expression level showed poor survival. Univariate and multivariate cox regression analysis further identified SSTR5-AS1 expression as a poor independent prognostic factor for PCa patients. Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine incorporation assay, wound-healing assay and Transwell assay were performed to investigate the functional role of SSTR5-AS1 in PCa cells. The in vitro results indicated that SSTR5-AS1 knockdown inhibited, while SSTR5-AS1 overexpression promoted the proliferation, migration, and invasion of PCa cells. At molecular level, SSTR5-AS1 knockdown downregulated the protein levels of proliferating cell nuclear antigen, N-cadherin and vimentin, and upregulated E-cadherin expression in PC-3 cells. SSTR5-AS1 overexpression obtained opposite results on these protein markers in DU145 cells. In conclusion, these findings indicated that SSTR5-AS1 promotes PCa cell behaviors, which might provide a potential therapeutic target for PCa patients.

Gouty arthritis (GA), one of the most common forms of inflammatory arthritis, is characterized by elevated serum uric acid concentrations and the consequent deposition of monosodium urate crystals. Under low-grade inflammatory stress, cells tend to adapt to the microenvironment by reprogramming their metabolic pathways. Here we review the aberrant metabolic responses to the inflammatory environment in immune and tissue cells in distinct phases of GA. Regulation of these pathways is implicated in metabolic alterations including mitochondrial dysfunction, changes in the glycolytic pathway, and alteration of lipid, uric acid, and bone metabolism among others. Investigations of how these alterations lead to proinflammatory and anti-inflammatory effects in each period of GA have revealed links to its pathogenesis. Knowledge gained may open up new opportunities for diagnosis, treatment and prognosis of GA and offer rationale for further investigation into the mechanisms underlying the progression of the disease.

Non-small-cell lung cancer (NSCLC) is a malignancy with high overall morbidity and mortality due to a lack of reliable methods for early diagnosis and successful treatment of the condition. We identified genes that would be valuable for the diagnosis and prognosis of lung cancer. Common DEGs (DEGs) in three GEO datasets were selected for KEGG and GO enrichment analysis. A protein-protein interaction (PPI) network was constructed using the STRING database, and molecular complex detection (MCODE) identified hub genes. Gene expression profiling interactive analysis (GEPIA) and the Kaplan-Meier method analyzed hub genes expression and prognostic value. Quantitative PCR and western blotting were used to test for differences in hub gene expression in multiple cell lines. The CCK-8 assay was used to determine the IC50 of the AURKA inhibitor CCT137690 in H1993 cells. Transwell and clonogenic assays validated the function of AURKA in lung cancer, and cell cycle experiments explored its possible mechanism of action. Overall, 239 DEGs were identified from three datasets. AURKA, BIRC5, CCNB1, DLGAP5, KIF11, and KIF15 had shown great potential for lung cancer diagnosis and prognosis. In vitro experiments suggested that AURKA significantly influenced the proliferation and migration of lung cancer cells and activities related to the dysregulation of the cell cycle. AURKA, BIRC5, CCNB1, DLGAP5, KIF11, and KIF15 may be critical genes that influence the occurrence, development, and prognosis of NSCLC. AURKA significantly affects the proliferation and migration of lung cancer cells by disrupting the cell cycle.