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Updated: Sep 5, 2025

Clinicopathological Analysis of miRNA Expression in Breast Cancer Tissues by Using miRNA In Situ Hybridization
Published on: June 7, 2016
Identification of expression of CCND1-related lncRNAs in breast cancer
Bashdar Mahmud Hussen1, Hazha Jamal Hidayat2, Soudeh Ghafouri-Fard3
1Department of Biology, College of Education, Salahaddin University-Erbil, Kurdistan Region, Iraq; Department of Pharmacognosy, College of Pharmacy, Hawler Medical University, Kurdistan Region, Iraq.
Abstract:
Cyclin D1 has been shown to participate in the pathogenesis of breast cancer. This cell cycle-related protein has direct or indirect interactions with long non-coding RNAs (lncRNAs). In the present two-step study, we first identified CCND1-related lncRNAs through an in silico approach. Then, we measured expression of CCND1 mRNA and five lncRNAs in paired breast cancer samples and their matched non-cancerous samples obtained from adjacent tissues. HOTTIP expression was significantly higher in breast cancer tissues compared with adjacent tissues (expression ratio (95% CI)= 4.63 (1.56-13.76), P value= 0.0070). Similarly, CBR3-AS1 was up-regulated in cancerous tissues compared with control tissues (expression ration (95% CI)= 3.26 (1.35-7.86), P value= 0.0122). Expression of HOTTIP was higher in estrogen receptor (ER) negative samples compared with ER positive ones (-4.35 ± 1.33 versus -4.63 ± 0.62, P value=0.002). CBR3-AS1 could differentiate between these two sets of samples with AUC±SD, sensitivity, specificity and P values of 0.7 ± 0.05, 0.9, 0.49 and 0.003, respectively. These values were 0.68 ± 0.04, 0.87, 0.34 and 0.04 for HOTTIP. Although we could not find difference in expression of CCND1 between these two sets of samples, we reported up-regulation of two CCND1-related lncRNAs in breast cancer samples. These lncRNAs are putative markers for breast cancer.
Insights
Two long non-coding RNAs (lncRNAs), HOTTIP and CBR3-AS1, are upregulated in breast cancer tissues. These CCND1-related lncRNAs show potential as diagnostic markers for breast cancer, especially in distinguishing estrogen receptor negative cases.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cyclin D1 (CCND1) plays a role in breast cancer pathogenesis.
- Long non-coding RNAs (lncRNAs) are implicated in cancer development and can interact with proteins like CCND1.
Purpose of the Study:
- To identify CCND1-related lncRNAs.
- To investigate the expression levels of CCND1 mRNA and selected lncRNAs in breast cancer.
- To evaluate the potential of these lncRNAs as breast cancer biomarkers.
Main Methods:
- In silico identification of CCND1-related lncRNAs.
- Quantitative measurement of CCND1 mRNA and five lncRNAs in paired breast cancer and adjacent non-cancerous tissues.
- Analysis of lncRNA expression in relation to estrogen receptor (ER) status.
Main Results:
- HOTTIP and CBR3-AS1 were significantly upregulated in breast cancer tissues compared to adjacent non-cancerous tissues.
- HOTTIP expression was higher in ER-negative breast cancer samples.
- CBR3-AS1 and HOTTIP demonstrated potential in differentiating between sample types, with CBR3-AS1 showing higher diagnostic accuracy.
Conclusions:
- The study identified HOTTIP and CBR3-AS1 as upregulated CCND1-related lncRNAs in breast cancer.
- These lncRNAs may serve as potential biomarkers for breast cancer diagnosis and prognosis.
- Further research is warranted to explore their clinical utility.
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