Objective: Circular RNAs (circRNAs) are involved in regulating of carcinogenesis of various cancer cells. However, the function of circRNAs in colorectal cancer (CRC) has remained largely unknown. This study investigated the characteristic expression of circRNAs in CRC and adjacent normal tissues, analyzed the miRNAs related to candidate circRNAs, and studied the correlation between circRNAs with clinical data of CRC. Methods: Human CircRNA microarray has been applied to screen the expressions of circRNAs of the CRC tissues and adjacent normal tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) verified the candidate circRNAs in CRC tissue and patients’ peripheral blood. The circRNA array data were analyzed by GeneSpring 13.0 (Agilent) software. The diseases, pathways and functional enrichment analysis of these genes were performed using the KEGG system. In addition, the circRNA-miRNA network was constructed based on the miRanda-3.3 software. Statistical analysis was performed with SPSS23.0, GraphPad Prism, and Sigmaplot software. Results: In total, 13,198 circRNAs were identified as distinct between CRC and adjacent normal tissues, including 6,697 upregulated and 6,501 downregulated genes. Based on scores, six of them were selected for further verification in CRC tissues and peripheral blood. The hsa_circ_0004585 expression was significantly upregulated both in CRC patients tissue and peripheral blood. Hsa_circ_0004585 was positively correlated with patient’s tumor size, indicating the function of hsa_circ_0004585 in CRC carcinogenesis and metastasis. Conclusion: Hsa_circ_0004585 could be a potential biomarker for diagnosis of CRC.
Background: To study the specific expression of circular RNA (circRNA) in breast cancer and adjacent normal tissues to identify differentially expressed circRNA in breast cancer patients. To study the correlation between circRNA and clinical data of breast cancer, and to evaluate its potential as a breast cancer biomarker. Methods: The differential expression of circRNAs between the breast cancer tissues and adjacent normal tissues was screened by Human CircRNA Microarray. Candidate circRNAs verified by qRT-PCR. CircRNA was analyzed by Agilent GeneSpring 13.0 software. SPSS23.0, GraphPad Prism, and Sigmaplot software were used for statistical analysis. Perform T test, one-way ANOVA, curve regression analysis and ROC curve analysis for evaluating the diagnostic value of circular RNA. Results: Among the 2021 differentially expressed circRNAs, 546 were up-regulated and 1475 were down-regulated in breast cancer tissues. The validation study demonstrated that six circRNAs were downregulated. Among them, hsa_circ_0104824 proved high correlation between breast cancer tissues and plasma samples in its expression and diagnostic value. Conclusion: Hsa_circ_0104824 may serve as a promising predictive biomarker and therapeutic target for patients with breast cancer.
Homoharringtonine (HHT), a natural alkaloid derived from the cephalotaxus, exhibited its anti-cancer effects in hematological malignancies clinically. However, its pesticide effects and mechanisms in treating solid tumors remain unclear. In this study, we found that HHT was capable of inhibiting tumor growth after 5-days treatment of breast cancer cells, MCF-7, in vivo. Furthemore, HHT also significantly inhibited the cancer cell growth and induced cell apoptosis in vitro. miRNA sequencing proved miR-18a-3p was noticeably downregulated in the cells after HHT treatment. Moreover, downregulating miR-18a-3p increased HHT-induced cell apoptosis; our data supported that HHT suppressed miR-18a-3p expression and inhibited tumorigenesis might via AKT-mTOR signaling pathway. In conclusion: our study proved that HHT suppressed breast cancer cell growth and promoted apoptosis mediated by regulating of the miR-18a-3p-AKT-mTOR signaling pathway, HHT may be a promising antitumor agent in breast cancer treatment.
Breast cancer (BC) is one of the commonly occurring malignancies in females worldwide. Despite significant advances in therapeutics, the mortality and morbidity of BC still lead to low survival and poor prognosis due to the drug resistance. There are certain chemotherapeutic, endocrine, and target medicines often used for BC patients, including anthracyclines, taxanes, docetaxel, cisplatin, and fluorouracil. The drug resistance mechanisms of these medicines are complicated and have not been fully elucidated. It was reported that non-coding RNAs (ncRNAs), such as micro RNAs (miRNA), long-chain non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) performed key roles in regulating tumor development and mediating therapy resistance. However, the mechanism of these ncRNAs in BC chemotherapeutic, endocrine, and targeted drug resistance was different. This review aims to reveal the mechanism and potential functions of ncRNAs in BC drug resistance and to highlight the ncRNAs as a novel target for achieving improved treatment outcomes for BC patients.
Kidney cancers including clear cell carcinoma (RCC) are identified with very vulnerable mitochondria DNA (mtDNA) and frequent epigenetic aberrations. Bone metastasis from RCC is prevalent and destructive. Bone marrow contains a quite hypoxic microenvironment that usually insitigate 50% of hypermethylation events in conferring a selective advantage for tumor growth. We hypothesized that hypermethylation of mtDNA in RCC cells would significantly contribute to bone metastatic tumor progression. Methylation-specific polymerase chain reaction assay (MSP) was adopted to measure the methylation status of D-loop region of mtDNA in 15 pairs of bone metastatic and primary RCC as well as tumor adjescent normal kidney tissues. mtDNA copy number was examined by the real-time quantitative polymerase chain reaction (qPCR). Western blotting analysis was used to measure the accumulation of several DNA methyltransferases (DNMTs) in the mitochondria and nucleus fractions of bone metastatic RCC cells. mRNA expression of mitochondria encoded genes was examined by RT-PCR. Reactive oxygen species (ROS), mitochondrial membrane potential and ATP content were measured using in vitro cells treated with de-methylation drug 5-Azacytidine (5-Aza). Non-invasive bioluminescent imaging was performed to monitor tumor occurrence in skeleton in mice. Our results showed that the D-loop region in bone metastatic tumor cells was markedly hypermethylated than those in primary RCC tumor cells, that is associated with a decreased mtDNA copy number and accumulation of DNMT1 in the mitochondria. The bone-tropism tumor colonization and progression of RCC cells was significantly suppressed by demethylating the D-loop region of mtDNA and reducing the intracellular level of ROS and ATP by 5-Aza treatment. In conclusion, our study provided a direct association between hypermethylation of mtDNA in RCC with bone metastastic tumor growth.
This study provides evidence that men carrying shorter (<22) AR CAG repeats have lower HDL-C level and increased risk of hypertension. The androgenic activity may differ due to the polymorphic length of CAG repeats of the AR gene.
Background : To investigate the characteristic expression of circular RNAs between breast cancer and para-carcinoma tissue, identified hsa-circ-000696 as a novel biomarker for breast cancer. Methods: 136 patients were recruited in General Hospital of NingXia Medical Universit. Of which 3 patients tissue for microarray analysis, 20 and 113 patients for circRNA expression in tissue and peripheral blood, respectively. The candidate circRNAs was verified by qPCR in BC patients’ tissue and peripheral blood. GeneSpring 13.0(Agilent) software were used for analysis the circRNA array data. CircRNA structure were performed by circPrimer1.2 software. MiRanda v3.3,RNAhybrid 2.1 and Cytoscape 3.6.0 were utilized as tools to predict the circRNA-miRNA networks. T-test, Curve regression analysis and ROC analysis were performed to determine the diagnostic values of candidate circRNAs. Statistical analysis was performed using SPSS23.0 software. Results: 2021 differentially expressed circRNAs were identified, of which 546 were upregulated and 1475 were downregulated. Four circRNAs were selected with filter criteria for further verify in BC tissues. Hsa-circ-0006969 was significantly downregulated both in breast cancer tissues and peripheral blood. Hsa-circ-0006969 proved a highest diagnostic value in breast cancer tissues(AUC=0.889), peripheral blood(AUC=0.823) for Grade 1(AUC=0.672), Grade 3(AUC=0.675), ER positive(AUC=0.648), TNM Ⅰ(AUC=0.687) and TNM Ⅱ(AUC=0.769), TNM Ⅲ(AUC=0.757), TNM early stage(Ⅰ, Ⅱ) (AUC=0.751). Hsa-circ-0006969 show more effective diagnostic values of for tumor metastasis (AUC=0.742) compared with CA153 (AUC=0.712). Conclusion: Has-circ-0006969 could be a novel predictive biomarker for diagnostic and treatment of breast cancer.
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