Critical Reviews in Eukaryotic Gene Expression最新文献

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.

Hepatocellular carcinoma (HCC) is one common cancer in the world. Previous studies have shown that miR-17 family members are elevated in most tumors and promote tumor progression. However, there is no comprehensive analysis of the expression and functional mechanism of the microRNA-17 (miR-17) family in HCC. The aim of this study is to comprehensively analyze the function of the miR-17 family in HCC and the molecular mechanism of its role. Bioinfoimatics analysis of the miR-17 family expression profile and its relationship to clinical significance using The Cancer Genome Atlas (TCGA) database, and this result was confirmed using quantitative real-time polymerase chain reaction. miR-17 family members were tested for functional effects through transfection of miRNA precursors and inhibitors, and monitoring cell viability and migration by cell count and wound healing assays. In addition, we using dual-luciferase assay and Western blot demonstrated the targeting relationship between the miRNA-17 family and RUNX3. These members of miR-17 family were highly expressed in HCC tissues, and the overexpression of the miR-17 family promoted the proliferation and migration of SMMC-7721 cells, whereas treatment with anti-miR17 inhibitors caused the opposite effects. Notably, we also found that inhibitors anti-each member of miR-17 can suppress the expression of the entire family member. In addition, they can bind to the 3' untranslated region of RUNX3 to regulate its expression at the translational level. Our results proved that miR-17 family has oncogenic characteristics, overexpression every member of the family contributed to HCC cell proliferation and migration by reducing the translation of RUNX3.

Non-small-cell lung cancer (NSCLC) is the major subtype of lung cancer, with a series of long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and proteins involved in its pathogenesis. This study sought to investigate the functionality of lncRNA EPB41L4A antisense RNA 1 (lncRNA EPB41L4A-AS1) in the proliferation of NSCLC cells and provide a novel theoretical reference for NSCLC treatment. Levels of lncRNA EPB41L4A-AS1, miR-105-5p, and GTPase, IMAP family member 6 (GIMAP6) in tissues and cells were measured by RT-qPCR and the correlation between lncRNA EPB41L4A-AS1 and clinicopathological characteristics was analyzed. Cell proliferation was evaluated by cell counting kit-8 and colony formation assays. The subcellular localization of lncRNA EPB41L4A-AS1 was analyzed by the subcellular fractionation assay and the binding of miR-105-5p to lncRNA EPB41L4A-AS1 or GIMAP6 was analyzed by dual-luciferase and RNA pull-down assays. Functional rescue experiments were performed to analyze the role of miR-105-5p/GIMAP6 in NSCLC cell proliferation. lncRNA EPB41L4A-AS1 and GIMAP6 were downregulated while miR-105-5p was upregulated in NSCLC tissues and cells. lncRNA EPB41L4A-AS1 was correlated with tumor size and clinical staging and its overexpression reduced NSCLC cell proliferation. lncRNA EPB41L4A-AS1 was negatively correlated with miR-105-5p and positively correlated with GIMAP6 in NSCLC tissues, and lncRNA EPB41L4A-AS1 sponged miR-105-5p to promote GIMAP6 transcription in NSCLC cells. Overexpression of miR-105-5p or knockdown of GIMAP6 reversed the inhibition of lncRNA EPB41L4A-AS1 overexpression on NSCLC cell proliferation. lncRNA EPB41L4A-AS1 was downregulated in NSCLC and mitigated NSCLC cell proliferation through the miR-105-5p/GI-MAP6 axis.

As an autophagy inhibitor, chloroquine (CQ) showed anti-tumor effect on several types of cancer and paclitaxel (PTX) is widely used in the treatment of esophageal carcinoma patients, but chemoresistance remains a major hurdle for PTX application due to the cytoprotective autophagy. Therefore, the aim of this study was to investigate whether CQ could elevate the anti-tumor effect of PTX on esophageal carcinoma cell line EC109 and explore the potential molecular mechanisms. We confirmed the suppressive effect of PTX on EC109 by MTT, scratch test, transwell and soft agar assay. And, we detected the key proteins in Akt/mTOR pathway, as well as the autophagy marker LC3 and p62 through Western Blot. In addition, GFP-LC3 plasmid was transfected into EC109 cells to monitor the autophagosome after CQ and PTX treatment. Ultimately, we observed the alterations in the proliferation and colony formation abilities of EC109 after knocking down mTOR by shRNA. We confirmed PTX could suppress the proliferation, migration and colony formation (all P < 0.05) abilities of EC109, and CQ could sensitize the inhibition effect of PTX by inhibiting autophagy through Akt/mTOR pathway. Furthermore, inhibiting Akt/mTOR pathway initiated autophagy and enhanced the sensitivity of EC109 to CQ and PTX. In summary, we suggest CQ could be used as a potential chemosensitizer for PTX in esophageal carcinoma treatment.

The objective of this study was to determine the regulatory mechanism of MAGI2-AS3 in clear cell renal cell carcinoma (ccRCC), thereby supplying a new insight for ccRCC treatment. Expression data in TCGA-KIRC were obtained. Target gene lncRNA for research was determined using expression analysis and clinical analysis. lncRNA's downstream regulatory miRNA and mRNA were predicted by bioinformatics databases. ccRCC cell malignant phenotypes were detected via CCK-8, colony formation, Transwell migration, and invasion assays. The targeting relationship between genes was assessed through dual-luciferase reporter gene analysis. Kaplan-Meier (K-M) analysis was carried out to verify the effect of MAGI2-AS3, miR-629-5p, and PRDM16 on the survival rate of ccRCC patients. MAGI2-AS3 expression in ccRCC tissue and cells was shown to be markedly decreased and its expression to continuously decline with tumor progression. MAGI2-AS3 suppresses ccRCC proliferation and migration. Dual-luciferase assay showed that MAGI2-AS3 binds miR-629-5p and that miR-629-5p binds PRDM16. In addition, functional experiments showed that MAGI2-AS3 facilitates PRDM16 expression by repressing miR-629-5p expression, thereby suppressing ccRCC cell aggression. K-M analysis showed that upregulation of either MAGI2-AS3 or PRDM16 significantly improves ccRCC patient survival, while upregulation of miR-629-5p has no significant impact. MAGI2-AS3 sponges miR-629-5p to modulate PRDM16 to mediate ccRCC development. Meanwhile, the MAGI2-AS3/miR-629-5p/PRDM16 axis, as a regulatory pathway of ccRCC progression, may be a possible therapeutic target and prognostic indicator of ccRCC.