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Published on: March 30, 2019
Long noncoding RNA and mRNA profiling in MDA-MB-231 cells following RNAi-mediated knockdown of SIRT7
Kun-Lin Chen1, Lian Li1, Yi-Ru Wang1
1Animal Genetics, Breeding and Reproduction Department, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, People's Republic of China.
Abstract:
Breast cancer is one of the most common malignant cancers among women and a major clinical obstacle. Although studies have reported the abnormal expression of SIRT7 in breast cancer, whether the function of SIRT7 regulates the expression of long noncoding RNAs (lncRNAs) in breast cancer remains unknown. We aimed to determine the differential expressions of mRNAs and lncRNAs associated with SIRT7 and understand the regulatory mechanism of SIRT7 in breast cancer. RNA sequencing was performed to explore the transcriptome in MDA-MB-231 cells after SIRT7 depletion, and a total of 50,634 different transcripts were identified. In comparison with the negative control, siSIRT7 groups showed 240 differentially expressed mRNAs and 26 differentially expressed lncRNAs. Gene ontology analysis revealed that the differentially expressed mRNAs mainly regulated DNA replication, CXCR chemokine receptor binding, and maturation of large subunit rRNA from tricistronic rRNA transcript, nucleoplasm, mitochondrion, and NAD+ ADP-ribosyltransferase activity. Kyoto Encyclopedia of Genes and Genomes analysis showed that the differentially expressed mRNAs were mainly involved in pathways associated with MAPK signaling pathway, tumor necrosis factor signaling pathway, hepatitis B, and cancer. Moreover, the target genes of the differentially expressed lncRNAs mainly regulated the carboxylic acid metabolic processes and were involved in glycolysis pathway. The mRNA-lncRNA coexpression network comprised 186 mRNAs and 23 lncRNAs. Our results provide essential data regarding differentially expressed lncRNAs and mRNAs after the depletion of SIRT7 in breast cancer cells, which may be useful to elucidate the role of SIRT7 in breast cancer development.
Insights
This study reveals how SIRT7 influences gene expression in breast cancer. Depleting SIRT7 altered messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs), impacting key cellular processes and cancer pathways.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Breast cancer is a leading cause of death in women worldwide.
- Sirtuin 7 (SIRT7) is frequently dysregulated in breast cancer, but its regulatory role in gene expression, particularly long noncoding RNAs (lncRNAs), remains unclear.
Purpose of the Study:
- To investigate the differential expression of messenger RNAs (mRNAs) and lncRNAs following SIRT7 depletion in breast cancer cells.
- To elucidate the regulatory mechanisms of SIRT7 in breast cancer development by analyzing transcriptomic changes.
Main Methods:
- RNA sequencing was employed to profile the transcriptome of MDA-MB-231 breast cancer cells after SIRT7 knockdown.
- Bioinformatic analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, were performed on differentially expressed genes.
- An mRNA-lncRNA coexpression network was constructed to identify potential regulatory interactions.
Main Results:
- SIRT7 depletion resulted in the differential expression of 240 mRNAs and 26 lncRNAs.
- Differentially expressed mRNAs were associated with DNA replication, chemokine receptor binding, rRNA processing, and NAD+ ADP-ribosyltransferase activity.
- KEGG analysis indicated involvement in MAPK signaling, tumor necrosis factor signaling, and cancer pathways; lncRNA targets were linked to carboxylic acid metabolism and glycolysis.
Conclusions:
- SIRT7 plays a significant role in regulating mRNA and lncRNA expression in breast cancer cells.
- The identified differentially expressed transcripts and pathways provide insights into SIRT7's function in breast cancer pathogenesis.
- These findings offer potential targets for understanding and treating breast cancer.
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