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Aberrantly expressed mRNAs and long non-coding RNAs in patients with invasive ductal breast carcinoma: a pilot study.

ABSTRACT: Invasive ductal breast carcinoma (IDBC) is the most prevalent type of invasive breast cancer in females; however, the pathogenesis of IDBC remains to be elucidated. Therefore, the identification of novel markers may enhance current understanding of the initiation and development of IDBC as well as elucidate potential therapeutic targets for effective treatment of IDBC. In the present study, a pilot study was conducted to screen for potential mRNAs and long non?coding (lnc)RNAs that exhibit aberrantly altered expression in patients with IDBC. Fresh breast cancer specimens and normal breast tissues were obtained from three female patients with IDBC aged ?60 years following a modified radical mastectomy without chemotherapy. Expression levels of 44,244 probes were detected and included in the analysis, of which 22,078 (49.9%) were mRNAs and 22,166 (50.1%) were lncRNAs. Potential marker screening was performed using paired t?tests (criterion 1), false discovery rates (FDR; criterion 2) and sure independence screening procedures based on distance correlations (DC?SIS; criterion 3). The results showed that in IDBC tissues 3,510 probes had a ?2?fold statistically significant change in expression levels compared to those in the corresponding normal breast tissue (P<0.05); in addition, following FDR analysis, 353 probes were found to have significantly altered expression levels. Furthermore, DC?SIS analysis identified 18 probes (12 mRNA and 6 lncRNAs) with significantly altered expression levels in IDBC tissue; these 18 probes therefore demonstrated significant results in all three criteria. Several of the mRNAs identified have been previously reported to be involved in signal transduction, protein binding, and cancer pathways, and the present study revealed that the majority of their gene products were located in the cytoplasm. Two of the six identified lncRNAs demonstrated a >10?fold decrease in expression levels in IDBC tissues compared to that in the normal breast tissue. However, further studies are required in order to elucidate the biological functions of the identified probes.

SUBMITTER: Chen X

PROVIDER: S-EPMC4440223 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Aberrantly expressed mRNAs and long non-coding RNAs in patients with invasive ductal breast carcinoma: a pilot study.

Chen Xuedong X Yang Jingyun J Qian Liyuan L Cao Tianzhu T

Molecular medicine reports 20141120 3

Invasive ductal breast carcinoma (IDBC) is the most prevalent type of invasive breast cancer in females; however, the pathogenesis of IDBC remains to be elucidated. Therefore, the identification of novel markers may enhance current understanding of the initiation and development of IDBC as well as elucidate potential therapeutic targets for effective treatment of IDBC. In the present study, a pilot study was conducted to screen for potential mRNAs and long non‑coding (lnc)RNAs that exhibit aberr ...[more]

PMID: 25411894

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Project description:Long non-coding RNAs (lncRNAs) are closely associated with the regulation of various biological processes and are involved in the pathogenesis of numerous diseases. However, to the best of our knowledge, the role of lncRNAs in ventilator‑induced lung injury (VILI) has yet to be evaluated. In the present study, high‑throughput sequencing was applied to investigate differentially expressed lncRNAs and mRNAs (fold change >2; false discovery rate <0.05). Bioinformatics analysis was employed to predict the functions of differentially expressed lncRNAs. A total of 104 lncRNAs (74 upregulated and 30 downregulated) and 809 mRNAs (521 upregulated and 288 downregulated) were differentially expressed in lung tissues from the VILI group. Gene ontology analysis demonstrated that the differentially expressed lncRNAs and mRNAs were mainly associated with biological functions, including apoptosis, angiogenesis, neutrophil chemotaxis and skeletal muscle cell differentiation. The top four enriched pathways were the tumor necrosis factor (TNF) signaling pathway, P53 signaling pathway, neuroactive ligand‑receptor interaction and the forkhead box O signaling pathway. Several lncRNAs were predicted to serve a vital role in VILI. Subsequently, three lncRNAs [mitogen‑activated protein kinase kinase 3, opposite strand (Map2k3os), dynamin 3, opposite strand and abhydrolase domain containing 11, opposite strand] and three mRNAs (growth arrest and DNA damage‑inducible α, claudin 4 and thromboxane A2 receptor) were measured by reverse transcription‑quantitative polymerase chain reaction, in order to confirm the veracity of RNA‑sequencing analysis. In addition, Map2k3os small interfering RNA transfection inhibited the expression of stretch‑induced cytokines [TNF‑α, interleukin (IL)‑1β and IL‑6] in MLE12 cells. In conclusion, the results of the present study provided a profile of differentially expressed lncRNAs in VILI. Several important lncRNAs may be involved in the pathological process of VILI, which may be useful to guide further investigation into the pathogenesis for this disease.

Project description:BackgroundCadmium (Cd) exposure has been found to have detrimental effects on the development of the central nervous system and cognitive ability in children. However, there is ongoing debate regarding the impact of maternal Cd exposure on the cognitive ability of offspring. In this study, we aimed to investigate the mechanisms underlying the influence of maternal Cd exposure on the cognitive ability of offspring rats.MethodsHere, we constructed a model of cadmium poisoning in first-generation rats through gavage. The cognitive and memory abilities of its offspring were evaluated by water maze experiment. Then, we used the gene chip to find out the key genes, and we performed qRT-PCR detection of these genes. Subsequently, enrichment analysis was employed to identify pathways. Finally, we constructed a co-expression network consisting of LncRNAs and mRNAs to elucidate the biological functions and regulatory mechanisms of LncRNAs.ResultsThe results of the water maze trial demonstrated that the offspring of rats exposed to cadmium in the first generation had reduced cognitive and memory abilities. Through an analysis of gene expression in the hippocampus of the cadmium-treated rats' offspring and the control group, we identified a correlation between the islet secretion pathway and the cognitive impairment observed in the offspring. Utilizing various algorithms, we identified Cpa1 and Prss1 as potential key genes associated with the cognitive impairment caused by cadmium. The results of qRT-PCR demonstrated a decrease in the expression levels of these genes in the hippocampus of the cadmium-treated rats' offspring. In addition, in the co-expression network, we observed that Cpa1 was co-expressed with 11 LncRNAs, while Prss1 was associated with 4 unexplored LncRNAs. Furthermore, we conducted an analysis to examine the relationship between Cpa1, Prss1-related transcription factors, and LncRNAs.ConclusionOverall, this study provides novel insights into the molecular effects of first generation Cd exposure on the cognitive ability of offspring. The target genes and signaling pathways investigated in this study could serve as potential targets for improving neurodevelopment and cognitive ability in children.

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Aberrantly expressed mRNAs and long non-coding RNAs in patients with invasive ductal breast carcinoma: a pilot study.

Publications

Aberrantly expressed mRNAs and long non-coding RNAs in patients with invasive ductal breast carcinoma: a pilot study.

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