Abstract Background Breast cancer is a highly prevalent disease worldwide, and early diagnosis and treatment could reduce the mortality rate of breast cancer patients. microRNAs (miRNA) have been shown to regulate the occurrences and progression of many types of cancers. Thus, it is crucial to find novel biomarkers in breast cancer. miR‐449c‐5p acted as a biomarker in non‐small cell lung cancer, gastric carcinoma, and so forth. ERBB2 is an ideal target for breast cancer therapy. However, the molecular mechanisms between miR‐449c‐5p and ERBB2 in breast cancer remain poorly understood. Our study focused on the regulatory role of miR‐449c‐5p in breast cancer and its targeting relationship with ERBB2. Methods The miR‐449c‐5p expression in breast cancer tissue and normal tissue was searched from the online database (Starbase). The clinical prognosis of miR‐449c‐5p and ERBB2 was predicted by using the Kaplan–Meier analysis method. The expression of miR‐449c‐5p mimics and inhibitors was measured by qRT‐PCR. T47D cells were transfected with miR‐449c‐5p mimics and miR‐449c‐5p inhibitors. After that, CCK‐8, colony formation assays and Transwell assays were used to evaluate the cell proliferation ability, migration and invasion. Whether ERBB2 was the target gene of the miR‐449c‐5p was predicted by Starbase and verified by dual‐luciferase activity assay. In addition, protein levels and the relationship between signalling pathways were measured and validated using western blotting analysis. Results We confirmed that miR‐449c‐5p was highly expressed in breast cancer tissue, and its downregulation was linked with poor prognosis. Overexpression of miR‐449c‐5p inhibited the proliferation, migration and invasion of breast cancer cells. ERBB2 was a target of miR‐449c‐5p. The invasion, migration, and proliferation of breast cancer cells were inhibited by miR‐449c‐5p/ERBB2 through JAK‐STAT. Conclusion This study demonstrated that miR‐449c‐5p inhibits breast cancer cell proliferation, migration and invasion by targeting ERBB2 via JAK/STAT, which means miR‐449c‐5p, is a potential biomarker for breast cancer and provides a novel insight for diagnosis.
Breast cancer (BC) is the most frequently diagnosed cancer in women. Increasing evidence suggests that circular RNA (circRNA) exerts critical functions in BC progression. However, the roles of circRNA septin 9 (circSEPT9) in BC development and the underneath mechanism remain largely unclear so far. In this work, the RNA levels of circSEPT9, microRNA-149-5p (miR-149-5p) and solute carrier family 1 member 5 (SLC1A5) were detected by quantitative real-time polymerase chain reaction. Western blot was performed to check protein expression. Glutamine uptake, cell proliferation and cell apoptosis were investigated by glutamine uptake, cell counting kit-8, cell colony formation, 5-Ethynyl-29-deoxyuridine, flow cytometry analysis or DNA content quantitation assay. The interactions of miR-149-5p with circSEPT9 and SLC1A5 were identified by a dual-luciferase reporter assay. Mouse model assay was carried out to analyze the effect of circSEPT9 on tumor formation in vivo. Results showed that circSEPT9 and SLC1A5 expression were significantly upregulated, while miR-149-5p was downregulated in BC tissues and cells as compared with paracancerous normal breast tissues and human normal breast cells. Knockdown of circSEPT9 or SLC1A5 inhibited glutamine uptake and cell proliferation, but induced cell apoptosis in BC cells. SLC1A5 overexpression relieved circSEPT9 silencing-induced repression of BC cell malignancy. In mechanism, circSEPT9 regulated SLC1A5 expression by sponging miR-149-5p. In support, circSEPT9 knockdown led to delayed tumor tumorigenesis in vivo. In summary, these results indicates that circSEPT9 may act an oncogenic role in BC malignant progression by regulating miR-149-5p/SLC1A5 pathway, providing a novel mechanism responsible for BC development.
Precision medicine has been well recognized since it was proposed, and the invention of liquid biopsy meets the needs of this era. Circulating tumor DNA (ctDNA), one of the most promising components of liquid biopsies, has quickly become the focus of research in recent years because of its unique advantages in clinical application. This article reviews the clinical application of ctDNA in breast cancer detection in recent years and its potential clinical value.
Telomeres are DNA-protein complexes that protect eukaryotic chromosome ends from being erroneously repaired by the DNA damage repair system, and the length of telomeres indicates the replicative potential of the cell. Telomeres shorten during each division of the cell, resulting in telomeric damage and replicative senescence. Tumor cells tend to ensure cell proliferation potential and genomic stability by activating telomere maintenance mechanisms (TMMs) for telomere lengthening. The alternative lengthening of telomeres (ALT) pathway is the most frequently activated TMM in tumors of mesenchymal and neuroepithelial origin, and ALT also frequently occurs during experimental cellular immortalization of mesenchymal cells. ALT is a process that relies on homologous recombination (HR) to elongate telomeres. However, some processes in the ALT mechanism remain poorly understood. Here, we review the most recent understanding of ALT mechanisms and processes, which may help us to better understand how the ALT pathway is activated in cancer cells and determine the potential therapeutic targets in ALT pathway-stabilized tumors.
Background: Tumor-infiltrating lymphocytes have been reported to be associated with response to neoadjuvant chemotherapy and survival in breast cancer (BC) patients. However, little is known about the value of peripheral blood parameter in predicting the prognosis in BC. Methods: In this study, parameters of complete blood count from 417 BC patients with a median 7.6-year follow-up after surgery were collected and correlated with patient survival. Results: It was found that leukocyte counts were positively correlated with disease-free survival (DFS, p = 0.016) and overall survival (OS, p = 0.014), whereas platelet counts were negatively correlated with DFS (p = 0.003) and OS (p = 0.082) in BC. Leukocyte and platelet counts were independent prognostic factors for the BC patient survival. Besides, the prognostic value of leukocyte and platelet counts was further evaluated in the BC patients with different molecular subtypes. Together, BC patients with high leukocyte counts and low platelet counts had better DFS (p = 0.001) and OS (p = 0.017) than the other patients. Conclusion: Parameters of complete blood count could be acquired easily and serve as cost-effective prognostic biomarkers in BC.
Background CDH13 (cadherin 13) is a special cadherin cell adhesion molecule, and the methylation of its promoter causes inactivation in a considerable number of human cancers. To explore the association between CDH13 promoter methylation and breast cancer risk and prognosis, we systematically integrated published articles to investigate the diagnostic performance of the CDH13 methylation test for breast cancer. An independent DNA methylation microarray dataset from The Cancer Genome Atlas project (TCGA) project was used to validate the results of the meta-analysis. Methods The relevant literature was searched using the PubMed, Cochrane Library, Web of Science and Google Scholar databases for articles published in English up to May 2015. Data were analyzed using random effect or fixed effect models. The effect sizes were estimated by measuring an odds ratio (OR) or hazard ratio (HR) with a 95% confidence interval (CI). A chi-squared based Q test and sensitivity analysis were performed to examine the between-study heterogeneity and the contribution of single studies to the final results, respectively. Funnel plots were constructed to evaluate publication bias. Results Seven hundred and twenty-six breast tumor samples and 422 controls were collected from 13 published studies. The data from the TCGA set include both tumor and normal samples. A significant association was observed between CDH13 promoter methylation and breast cancer, with an aggregated OR equal to 13.73 (95%CI: 8.09~23.31, z = 9.70, p<0.0001) as measured using the fixed effect model and 14.23 (95%CI: 5.06~40.05, z = 5.03, p<0.0001) as measured using a random effect model. The HR values were calculated as 0.77 (95%CI: 0.27~2.21, z = -0.49, p = 0.622) and 0.38 (95%CI: 0.09~1.69, z = -1.27, p = 0.20) for overall survival (OS) and disease-free survival (DFS), respectively, using the random effect model. This result indicated that breast cancer patients with CDH13 promoter methylation correlated non-significantly with prognosis and is therefore similar to the findings of the TCGA project. Conclusions The methylation status of CDH13 promoter was strongly associated with breast cancer risk. However, CDH13 promoter methylation was not significantly related to the OS and DFS of breast cancer and may have limited prognostic value for breast cancer patients.
Objective To screen genes present in the whole process of colorectal tumor development, and to explore the molecular mechanism underlying the eolorectal adenoma-carcinoma sequence. Methods Affymetrix Human U133 PLAS 2. 0 GeneChip （covering 18400 transcripts, representing 14500 distinct genes） was used to compare different gene expression profiles between normal human colorectal mucosa, eolorectal adenoma, Dukes A, B and C-D eolorectal cancers. Results A total of 253 different ex- pressed genes among eolonrectal adenoma, Dukes A, B and C-D colorectal cancers were identified, among which 34 genes were consistently up-regulated （29 with known function, 5 unknown） , while 219 others were consistently down-regulated （ 196 with known function, 23 unknown）. Conclusion Onset and further tumor development of colorectal cancer is a complex evolutional course which involves numerous genes. These genes are expressed at the precancerous stage-colorectal adenoma, which indicates the potential of malignant transformation from normal colorectal cell into colorectal cancer is already in existence at the precancerosis, and these genes may participate in the whole process of colorectal carcinogenesis. Therefore, further analysis of obtained genes can help to elucidate the molecular pathogenesis of adenoma-cancer sequence, and is of guiding significance in the early diagnosis of colorectal cancer and a timely therapeutic intervention.
Key words:
Adenomatous polyposis coli; Adenocarcinoma; Gene expression chips; Gene expression profiling
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