Background: Long non-coding RNA (lncRNA) TatD DNase Domain Containing 1 (TATDN1) is a recently characterized oncogenic lncRNA in several types of cancer including breast cancer. Our preliminary microarray analysis revealed its upregulation in triple negative breast cancer (TNBC) and its inverse correlation with microRNA-26b (miR-26b), which is a tumor suppressive miRNA in breast cancer. This study was therefore carried out to investigate the interaction between TATDN1 and miR-26b in TNBC.
Methods: A total of 66 pairs of TNBC and non-tumor tissues were collected from 66 patients (45.8 ± 10.5 years old) with TNBC through biopsy under the guidance of MRI before initiation of any therapies. Quantitative reverse transcription PCR (RT-qPCR), transient cell transfection, methylation specific PCR (MSP) and cell proliferation assay were carried out in this study.
Results: We found that TATDN1 was upregulated and miR-26b was downregulated in TNBC. Correlation analysis showed that the expression of TATDN1 and miR-26b was inversely correlated. In TNBC cells, overexpression of TATDN1 mediated the downregulation of miR-26b. Knockdown of TATDN1 led to the upregulation of miR-26b. Methylation-specific PCR showed that TATDN1 positively regulated the methylation of miR-26b gene. Cell proliferation analysis showed that TATDN1 positively regulated the proliferation of TNBC cells. Overexpression of miR-26b attenuated the effects of TATDN1 overexpression on cell proliferation.
Conclusion: Therefore, overexpression of TATDN1 promotes cancer cell proliferation in TNBC by regulating the methylation of miR-26b gene.
Keywords: triple negative breast cancer, TATDN1, miR-26b, methylation, proliferation