LINC01116 affects patient survival differently and is dissimilarly expressed in ER+ and ER- breast cancer samples.

BACKGROUND: Breast cancer is the most commonly detected cancer and one of the leading causes of cancer mortality. Emerging evidence supports that aberrant expression of lncRNAs is correlated with tumor progression and various aspects of tumor development. AIM: This study aimed to evaluate the expression pattern of LINC01116 in breast cancer tissues and investigate the impact of LINC01116 on patients' survival. METHODS AND RESULTS: Microarray and qRT-PCR data analysis were performed, and the KM-plotter database was used in this study. In addition, the gain of function approach was performed to examine the effect of LINC01116 on breast cancer cells in-vitro. The results exhibited that LINC01116 is meaningfully upregulated in the ER+ tumor specimens compared to the ER- ones. Also, relative to normal tissues, the expression of LINC01116 in ER+ and ER- tumor tissues significantly increased and decreased, respectively. ROC curve analysis revealed the power of LINC01116 in distinguishing ER+ from ER- samples. Additionally, the Kaplan-Meier survival analysis showed that the LINC01116 expression positively correlates with survival probability in all as well as ER+ patients. However, this correlation was negative in ER- patients. Furthermore, our results showed that the overexpression of LINC01116 induces TGF-ß signaling in ER- cells (MDA-MB-231), and microarray data analysis revealed that LINC01116 is significantly upregulated in 17ß-Estradiol treated MCF7 cells. CONCLUSION: In conclusion, our results suggest that LINC01116 can be a potential biomarker in distinguishing ER+ and ER- tissues and has different effects on patients' survival based on ER status by affecting TGF-ß and ER signaling.

Clinical whole-exome sequencing analysis reveals a novel missense COL11A1 mutation resulting in an 18-week Iranian male aborted fetus with Fibrochondrogenesis 1: A case report.

Fibrochondrogenesis 1, an autosomal recessive syndrome, is a rare disease that causes short-limbed skeletal dysplasia. Mutations in the gene encoding the α1 chain of type XI collagen (COL11A1) are seen to be the main cause of this disease. We present an 18-week Iranian male aborted fetus with Fibrochondrogenesis 1 from consanguineous parents. Whole-exome sequencing revealed a novel missense variant from G to A in exon 45 of 68 in the COL11A1 gene (NM_080629.2: c.3440G > A, [p.G1147E, g.103404625]). The mutation was confirmed by Sanger sequencing and further, MutationTaster predicted this variant to be disease-causing. Bioinformatic analysis suggests that this variant is highly conserved in both nucleotide and protein levels, suggesting that it has an important function in the proper role of COL11A1 protein. In silico analysis suggests that this mutation alters the COL11A1 protein structure through a Glycine to Glutamic acid substitution.

miR-361-5p as a promising qRT-PCR internal control for tumor and normal breast tissues.

BACKGROUND: One of the most widely used evaluation methods in miRNA experiments is qRT-PCR. However, selecting suitable internal controls (IC) is crucial for qRT-PCR experiments. Currently, there is no consensus on the ICs for miRNA qRT-PCR experiments in breast cancer. To this end, we tried to identify the most stable (the least expression alteration) and promising miRNAs in normal and tumor breast tissues by employing TCGA miRNA-Seq data and then experimentally validated them on fresh clinical samples. METHODS: A multi-component scoring system was used which takes into account multiple expression stability criteria as well as correlation with clinical characteristics. Furthermore, we extended the scoring system for more than two biological sub-groups. TCGA BRCA samples were analyzed based on two grouping criteria: Tumor & Normal samples and Tumor subtypes. The top 10 most stable miRNAs were further investigated by differential expression and survival analysis. Then, we examined the expression level of the top scored miRNA (hsa-miR-361-5p) along with two commonly used ICs hsa-miR-16-5p and U48 on 34 pairs of Primary breast tumor and their adjacent normal tissues using qRT-PCR. RESULTS: According to our multi-component scoring system, hsa-miR-361-5p had the highest stability score in both grouping criteria and hsa-miR-16-5p showed significantly lower scores. Based on our qRT-PCR assay, while U48 was the most abundant IC, hsa-miR-361-5p had lower standard deviation and also was the only IC capable of detecting a significant up-regulation of hsa-miR-21-5p in breast tumor tissue. CONCLUSIONS: miRNA-Seq data is a great source to discover stable ICs. Our results demonstrated that hsa-miR-361-5p is a highly stable miRNA in tumor and non-tumor breast tissue and we recommend it as a suitable reference gene for miRNA expression studies in breast cancer. Additionally, although hsa-miR-16-5p is a commonly used IC, it's not a suitable one for breast cancer studies.