Long noncoding RNA (lncRNA) metallothionein 1 J, pseudogene (MT1JP) is downregulated in triple-negative breast cancer and upregulates microRNA-138 (miR-138) to downregulate hypoxia-inducible factor-1α (HIF-1α)

Abstract

ABSTRACT Triple-negative breast cancer (TNBC) is a highly invasive subtype of breast cancer. This study explored the molecular mechanism and influences of metallothionein 1 J, pseudogene (MT1JP), microRNA-138 (miR-138), and hypoxia-inducible factor-1α (HIF-1α) on TNBC cell proliferation and migration. We confirmed TNBC cases by immunohistochemistry (IHC) staining. The expression of MT1JP in two types of tissue collected from 78 TNBC patients was detected by performing real-time quantitative fluorescence PCR (RT-qPCR). To further evaluate the relationship among MT1JP, miR-138 and HIF-1α, expression vectors of MT1JP and HIF-1α, as well as miR-138 mimic and inhibitor, were delivered into BT-549 cells. We observed that MT1JP was downregulated in TNBC. MT1JP was positively correlated with miR-138 but negatively correlated with HIF-1α in TNBC tissues. In TNBC cells, upregulation of miR-138 and downregulation of HIF-1α were observed after overexpression of MT1JP. In addition, overexpression of miR-138 resulted in downregulation of HIF-1α but did not affect the expression of MT1JP. Decreased proliferation rate of TNBC cells was observed after overexpression of MT1JP and miR-138. HIF-1α increased cell proliferation and migration. HIF-1α also suppressed the role of MT1JP and miR-138 in TNBC cell proliferation and migration. In conclusion, our findings demonstrated that MT1JP inhibited TNBC by regulating the miR-138/HIF-1α axis, indicating that MT1JP might serve as a biomarker or target for TNBC treatment.