ObjectiveTo summarize the latest progress of microRNA (miRNA or miR) in colorectal cancer (CRC)-related signaling pathways in the past three years, and provide new ideas for miRNA-targeted intervention or miRNA as tumor molecular markers for early diagnosis of CRC. MethodThe literature on the roles of miRNA in the CRC-related signaling pathways was retrieved and reviewed. ResultsMiRNAs were associated with cancers in nearly all critical pathways, which regulated almost all important signaling pathways associated with CRC. At present, the signaling pathways and miRNAs related to CRC mainly included Wnt-β-catenin (miR-520e, miR-8063, miR-576-5p, miR-142-3p, miR-19a-3p, miR-381, miR-411, miR-1205), phosphatidylinositol-3-kinaset-Akt (miR-19a, miR-493-5p, miR-3064-5p, mi-196b-5p, miR-3651), mitogen-activated protein kinase (miR-1288-3p, miR-3651, miR-152-3p), transforming growth factor-β (miR-183-5p, miR-21-5p, miR-195-5p, miR-581, miR-2911, miR-128-3p, let-7a), nuclear factor kappa B (miR-155, miR-129, miR-21), Janus kinase/signal transducers and activators of transcription (miR-198, miR-452, miR-128-3p, miR-495), Notch (miR-223, miR-10b, miR-449a), Hippo (miR-30a-5p, miR-375, miR-9), and Hedgehog (miR-372, miR-373), etc. signaling pathways. ConclusionsMiRNA play a role in one or more signaling pathways at the same time, and play an important regulatory role in the occurrence and development of CRC. MiRNAs have great potential as tumor markers in the diagnosis, treatment, and prognosis of colorectal cancer.
Breast cancer is a malignant tumor from normal breast epithelial. In recent years, many literature reports sought to determine the expression of predicted target genes of microRNA and their potential function, pathways and networks, which are involved in the tumorigenesis, metastasis and prognosis of breast cancer. The miR-21 has recently been found to be highly expressed in solid tumors than normal tissue, and it has exposed some layers of gene expression regulation that becomes a hot topic of breast cancer. This paper briefly reviews advances in research on miR-21 in breast cancer.
ObjectiveTo detect expressions of transient receptor potential channel C5 (TRPC5) and microRNA-320a (miR-320a) in thyroid cancer and explore clinical significances of them in thyroid cancer.MethodsThe expressions of TRPC5 and miR-320a mRNA in the thyroid cancer were investigated by searching the Ualcan database. While the expressions of TRPC5 and miR-320a mRNA in 80 cases of thyroid cancer, 35 cases of thyroid adenoma and 32 cases of normal thyroid tissues adjacent to thyroid adenoma tissues in the Zhengzhou Seventh People’s Hospital from March 2014 to March 2015 were tested. Real time PCR was used to detect the expressions of TRPC5 mRNA and miR-320a mRNA in the various tissues and Western blot was used to detect the TRPC5 protein in the thyroid cancer tissues. Therelationships between the expressions of TRPC5 and miR-320a mRNAs and clinicopathologic features of thyroid cancer were analyzed. The correlation between expressions of TRPC5 and miR-320a mRNA was analyzed by Pearson method. The risk factors influencing the prognosis were analyzed by univariate and multivariate Cox proportional hazards regression model.ResultsThe results of Ualcan database showed that the expression level of TRPC5 mRNA in the thyroid cancer was higher than that in the normal thyroid tissue (P<0.001), while the expression level of miR-320a mRNA was lower than that in the normal thyroid tissue (P<0.001). The results of clinical cases showed that the expression level of TRPC5 mRNA was significantly higher, while the expression of miR-320a mRNA was significantly lower in the thyroid cancer tissues as compared with the normal thyroid tissues (P<0.05). There was a negative correlation between the expression level of TRPC5 and miR-320a mRNA in the thyroid cancer (r=?0.653, P<0.001). The expressions of TRPC5 and miR-320a mRNA were correlated with the degree of differentiation, lymph node metastasis, and TNM stage (P<0.05). Kaplan-Meier survival curve analysis found that the patients with higher expression level of TRPC5 and lower expression level of miR-320a showed the poor prognosis, and multivariate analysis found that the lower tumor differentiation, later TNM stage, with lymph node metastasis, higher expression level of TRPC5 mRNA, and lower expression level of miR-320a mRNA were the risk factors affecting prognostic survival (P<0.05).ConclusionsFrom the database and clinical case data, it is concluded that TRPC5 mRNA is highly expressed, while miR-320a mRNA is lowly expressed in thyroid cancer tissues, and expressions of TRPC5 and miR-320a mRNA are related to degree of tumor differentiation, lymph node metastasis, TNM staging, and prognosis in patients with thyroid cancer. TRPC5 and miR-320a mRNA might be used as potential indicators for clinical and prognostic monitoring.
Objective To systematically evaluate the correlation between the expression of microRNA (miRNA)-21 and the prognosis of esophageal cancer. Methods PubMed, Cochrane Library, Embase, Wanfang Data, China National Knowledge Infrastructure and VIP Databases were searched by for the literature on the correlation between miRNA-21 and the prognosis of esophageal cancer till July 10, 2022. Two researchers independently performed literature screening, quality evaluation, and data extraction. Statistical analysis was conducted with Stata 14.0. Results A total of 13 articles were included, including 1 204 patients. The results of meta-analysis showed that: the overall survival (OS) of patients with high expression of miRNA-21 was lower than that of patients with low expression of miRNA-21 [hazard ratio (HR)=2.11, 95% confidence interval (CI) (1.56, 2.84), P<0.001]. miRNA-21 expression was not associated with disease free survival [HR=2.53, 95%CI (0.67, 8.22), P=0.182]. The OS of Asian patients with high expression of miRNA-21 was significantly lower [HR=2.44, 95%CI (1.71, 3.49), P=0.005], while the OS of non-Asian patients was not related to miRNA-21 expression [HR=1.34, 95%CI (0.94, 1.91), P=0.363]. The high expression of miRNA-21 was correlated with the decreased OS in patients with esophageal squamous cell carcinoma [HR=2.22, 95%CI (1.52, 3.26), P=0.001], while the OS in patients with esophageal adenocarcinoma was not correlated with the expression of miRNA-21 [HR=1.39, 95%CI (0.63, 3.06), P=0.409]. Conclusion The overexpression of miRNA-21 is associated with poor prognosis and might be regarded as a potential prognostic biomarker for patients with esophageal cancer.
MicroRNA (miRNA) is a noncoding RNA and protein involved in regulating gene expression in the transcription level. Epidermal growth factor receptor (EGFR) is a protein tyrosine kinase receptor and its mutations have been confirmed in non-small cell lung cancer (NSCLC) by a large number of studies in recent years. EGFR tyrosine kinase inhibitor (EGFR-TKI) is widely used for treatment of NSCLC patients with EGFR mutation. In recent years, miRNA is more and more important in tumor metastasis. The role of EGFR mutations in NSCLC has become a hot spot as well. New researches report that the relationship between miRNA and EGFR mutations plays an important role in NSCLC metastasis. Therefore, we write this review to discuss the mechanisms of miRNA and EGFR mutations in metastasis of NSCLC.
Objective To explore the effect of long non-coding RNA H19 (lncRNA H19) on chronic heart failure (CHF) rats and its possible mechanism. Methods CHF (SD male rats, with a weight of 300±10 g, 10 weeks old) rat model was established by abdominal aortic coarctation. The 84 rats successfully modeled were randomly divided into a model group, a si-NC group [transfected lncRNA H19 small interfering RNA (siRNA) negative control], a si-H19 group (transfected lncRNA H19 siRNA), a si-miR-NC group [transfected microRNA-214 (miR-214) siRNA negative control], a si-miR-214 group (transfected miR-214 siRNA), a si-H19+si-miR-NC group (co-transfected lncRNA H19 siRNA and miR-214 siRNA negative control), and a si-H19+si-miR-214 group (co-transfected lncRNA H19 siRNA and miR-214 siRNA), 12 rats in each group. Another 12 rats were set up in a sham operation group (rats were only threaded without ligation, and the other operations were the same as the model group). After 4 weeks of intervention, the cardiac function, serum myocardial injury markers, heart failure markers, inflammatory related factors, apoptosis related factors and myocardial histopathological changes were compared. The expressions of lncRNA H19 and miR-214 in myocardial tissue were detected by real-time fluorescence quantitative PCR, and the targeting relationship between lncRNA H19 and miR-214 was detected by double luciferase reporter gene. Results Compared with those in the sham operation group, the myocardium of rats in the model group was severely damaged and a large number of inflammatory cells infiltrated; the lncRNA H19, cardiac function indexes (left ventricular end systolic diameter, left ventricular end diastolic diameter), serum myocardial injury markers (creatine kinase MB, cardiac troponin I), heart failure markers (brain natriuretic peptide, N-terminal pro brain natriuretic peptide), inflammatory related factors (interleukin-1β, interleukin-18, tumor necrosis factor-α, interleukin-6), cardiomyocyte apoptosis rate, apoptosis related proteins [B lymphocytoma-2 (Bcl-2), Bcl-2 related X protein (Bax), cysteinyl aspartate specific proteinase-1 (Caspase-1)] in the myocardial tissue of the model group were significantly increased (P<0.05); miR-214 of myocardial tissue, cardiac function indexes (left ventricular ejection fraction, left ventricular fractional shortening) and Bcl-2/Bax ratio were significantly decreased (P<0.05). Compared with the model group, silencing lncRNA H19 could significantly improve the cardiac function and the changes of the above indexes in CHF rats, and reduce myocardial injury (P<0.05); down-regulation of miR-214 could significantly reverse the protective effect of si-H19 on myocardial injury in CHF rats (P<0.05). Conclusion Silencing lncRNA H19 can up-regulate the expression of miR-214, inhibit the expression of Caspase-1, inhibit the apoptosis and inflammatory reaction of cardiomyocytes, and alleviate myocardial injury in rats with CHF.
Objective To investigate the expression of miR-92a in breast cancer tissues and whether it can influence the migration and invasion ability of breast cancer cells through kruppel-like factor 4 (KLF4). Methods ① The expressions of miR-92a and KLF4 mRNA in cancer tissues and adjacent tissues were detected by qRT-PCR in 122 breast cancer patients who were operated in our hospital from May 2017 to October 2019. ② The expression of miR-92a in MCF-7 breast cancer cells was up-regulated or knocked out. Cell survival rate was detected by MTT assay, cell migration ability was detected by scratch assay, cell invasion ability was detected by Transwell assay, and the relative expression levels of KLF4, E-cadherin (E-cad), and N-cadherin (N-cad) proteins were detected by Western blotting. ③ The targeting relationship between miR-92a and KLF4 was detected by dual luciferase reporter gene assay. Results ① The relative expression levels of miR-92a and KLF4 mRNA in cancer tissues were higher than those in adjacent tissues (P<0.05). ② The up-regulation of miR-92a expression had no effect on the survival rate of MCF-7 breast cancer cells, but the migration and invasion ability of cells were enhanced (P<0.05). The knockdown of miR-92a expression decreased the survival rate of MCF-7 breast cancer cells and the ability of cell migration and invasion (P<0.05). ③ The miR-92a and KLF4 had a direct targeting relationship, up-regulation of miR-92a expression increased the relative expression levels of KLF4 and N-cad proteins, while decreased the relative expression level of E-cad protein (P<0.05). After knockout of miR-92a expression, the relative expression levels of KLF4 and N-cad proteins were decreased, while the relative expression level of E-cad protein was increased (P<0.05). Conclusion The miR-92a is highly expressed in breast cancer cells, and knockout of miR-92a expression can inhibit KLF4 signaling pathway and reduce the migration and invasion ability of breast cancer cells.
Colorectal cancer is one of the most common malignant diseases that threatens human being's health. With researches on microRNAs (miRNAs) getting deeper and wider, more evidences revealed that a great many of miRNAs have been involved in the development of colorectal cancer and have the potential to become the biomarker for early diagnosis, prediction of prognosis and recurrence of colorectal cancer. MiRNA-143/miRNA-145 are significantly reduced in several cancers, including colorectal cancer, showing an antitumorigenic activity. In the present article, we make a brief review on the advances in the researches on miRNA-143/miRNA-145 and colorectal cancer to provide guidance for further explorations of the mechanism and target therapy of this disease.
Objective To clarify the trends of expression levels of several up-regulated micro RNA (miRNA) in tissues of atrophic bone nonunion and mRNAs and proteins of their related target genes in osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs), and to explore their biological functions. Methods The hBMSCs were isolated from bone marrow of il iac bone by gradient centrifugation, and cultured. Osteogenic culture medium was used for osteogenic differentiation of the 4th generation of hBMSCs. The changes of corresponding miRNAs, mRNA and protein expression levels of related target genes were observed at 0 hour, 12 hours, 1 day, 2 days, 4 days, 7 days, and 14 days, by quantitative real-time PCR and Western blot. Results In the process of hBMSCs osteogenic differentiation, the mRNA and protein expression levels of osteoblastic target genes [alkal ine phosphatase l iver/bone/kidney (ALPL), bone morphogeneticprotein 2 (BMP-2), and platelet-derived factor alpha polypeptide (PDGF-A)] at most time points increased significantly whencompared with the values at 0 hour except that of BMP-2 decreased at 12 hours and 1 day, with maximum changes at 1 to 7 days. The miRNA expression levels, mRNA and protein expression levels changed significantly at different time points, while the trends of hsa-miRNA-149 and hsa-miRNA-654-5p changes were negatively correlated with the trends of ALPL and BMP-2 mRNA and protein expression changes respectively (P lt; 0.05). There was no obviously negative correlation between the trends of hsa-miRNA-221 change and PDGF-A change (P gt; 0.05). Conclusion In the osteogenic differentiation process of hBMSCs, hsa-miRNA-149 and hsa-miRNA-654-5p are closely related with the mRNA and protein regulation of ALPL and BMP-2, respectively.
