SEC14L3 plays a tumor-suppressive role in breast cancer through a Wnt/ß-catenin-related way.

Breast cancer, the most prevalent malignancy in women, is also the leading cause of cancer-related deaths in women worldwide. The activation of the Wnt pathway plays a pivotal role in the metastatic abilities of breast cancer. In this study, IL1F6, MRGPRX1, and SEC14L3 were significantly correlated to breast cancer patients'overall survival based on TCGA-BRCA dataset. Although IL1F6, MRGPRX1 and SEC14L3 high expression were associated with better survival in breast cancer patients, SEC14L3 had the biggest survival benefit for breast cancer; therefore, SEC14L3 was selected for the subsequent investigation. SEC14L3 mRNA expression and protein levels within breast cancer cell lines decreased compared with normal human breast epithelial cells. Overexpressing SEC14L3 in breast cancer cells inhibited the malignant phenotypes of cancer cells, including the capacity of cells to migrate and invade. SEC14L3 overexpression decreased the levels of mesenchymal markers, whereas SEC14L3 knockdown facilitated the malignant behaviors of breast cancer cells. SEC14L3 overexpression also inhibited Wnt/ß-catenin activation. The Wnt agonist strengthened the malignant phenotypes of breast cancer cells; moreover, the anti-tumor effects of SEC14L3 overexpression were partially attenuated by the Wnt agonist. Conclusively, SEC14L3, which is underexpressed in breast cancer cells and tissues, could play a tumor-suppressive role in a Wnt/ß-catenin-related way.

miRNA-192-5p impacts the sensitivity of breast cancer cells to doxorubicin via targeting peptidylprolyl isomerase A.

The administration of doxorubicin (DOX) is one of the first-line treatments of breast cancer. However, acquisition of resistance remains the major obstacle restricting the clinical application of DOX. MicroRNAs (miRNAs) are small, noncoding RNAs which play crucial role in epigenetic regulation. Recent studies have shown that miRNAs are associated with tumor chemoresistance. Here we aim to explore the role of miRNA-192-5p in resistance to DOX in breast cancer cells. Normal human breast epithelial cell line MCF-10A, breast cancer cell line Michigan Cancer Foundation-7 (MCF-7), and DOX-resistant breast cancer cell line MCF-7/ADR were used here. The expression of miR-192-5p was examined by qPCR, and the expression of peptidylprolyl isomerase A (PPIA) was examined by qPCR and Western blot. The effects of miR-192-5p overexpression on the sensitivity to DOX were confirmed by Methylthiazolyldiphenyl-tetrazolium bromide (MTT) and Annexin-V/PI assay. Downstream molecular mechanisms, including PPIA, BAD, CASP9, Bcl-2, and c-Jun N-terminal kinase (JNK) activation, were detected by Western blot and qPCR. Luciferase reporter assay was used to validate the association between miR-192-5p and PPIA. miR-192-5p was downregulated while PPIA was upregulated in MCF-7/ADR cells. Functionally, miR-192-5p overexpression increased sensitivity to DOX by promoting cell apoptosis. Mechanistically, miR-192-5p overexpression performed its function by activating JNK, augmenting BAD and caspase9 expression, and suppressing Bcl-2 and PPIA expression. Luciferase assay validated that PPIA was a direct target of miR-192-5p. miR-192-5p sensitizes breast cancer cells to DOX by targeting PPIA, suggesting that miR-192-5p might serve as a novel target for reversing DOX resistance and controlling breast tumor growth.