Abstract
BackgroundThe tumor suppressive role of miR-1296 is observed in triple negative breast cancer (TNBC). However, the effect of miR-1296-5p in ERBB2-positive breast cancers remains obscure.MethodsWhether ERBB2 was the target gene of the miR-1296-5p was predicted by online software, and determined by dual-luciferase activity assay. miR-1296-5p expression levels were determined in breast cancer samples (114 breast cancer tissues and 30 adjacent normal tissues) by using qRT-PCR. The effect of miR-1296-5p and inhibition of ERBB2/mTORC1 signaling on the downstream target was assessed by Western blot. SK-BR-3 and BT-474 breast cancer cell line was transfected with miR-1296-5p mimic after which cell proliferation and apoptosis were determined by the clonogenic assay and the flow cytometry system, respectively. In addition, the chemotherapeutic drug sensitivity of SK-BR-3 and BT-474 cells transfected with miR-1296-5p mimic were determined by MTT assay.ResultsThe luciferase assay carrying ERBB2 3′-untranslated region-based reporters expressed in SK-BR-3 and BT-474 cells suggested that ERBB2 was the target gene of miR-1296-5p. MiR-1296-5p was significantly decreased in breast cancer tissues compared to adjacent normal tissues. Moreover, it was declined in ERBB2-positive breast cancer samples compared with that in ERBB2-negative breast cancer tissues. Overexpressed miR-1296-5p reduced its target protein level and mTORC1/S6 activation, inhibited the proliferation of ERBB2-positive breast cancer cells and sensitized these cells to cisplatin and 5-fluorouracil-induced apoptosis.ConclusionsOur findings suggest that miR-1296-5p is involved in the regulation of proliferation in breast cancer cells via targeting ERBB2/mTORC1 signaling pathway.
Highlights
The tumor suppressive role of miR-1296 is observed in triple negative breast cancer (TNBC)
The miR-1296-5p mimics were transfected into SK-BR-3 or BT-474 cells and the expression levels of ERBB2 were examined by Western blot
We found that the expression of ERBB2 in miR-1296-5ptransfected cells was extremely depressed than that in control cells (Fig. 1d, e)
Summary
The tumor suppressive role of miR-1296 is observed in triple negative breast cancer (TNBC). The effect of miR-1296-5p in ERBB2-positive breast cancers remains obscure. Over-expressed ERBB2 couples to two MicroRNAs (miRNAs) have a wide range of ability to regulate cell survival, proliferation, differentiation, migration, invasion and metastasis of breast cancers [9,10,11]. In TNBC cells and tissues, miR1296 expression is significantly suppressed, and which sensitized TNBC cells to cisplatin treatment [15]. It is still largely unknown how specific miRNA functions affect ERBB2-positive breast cancers. We demonstrated that miR-1296-5p decreases the expression level of ERBB2 to inhibit the cell proliferation in ERBB2positive breast cancer
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