Long non-coding RNA LINC-PINT attenuates paclitaxel resistance in triple-negative breast cancer cells via targeting the RNA-binding protein NONO.

The treatment of triple-negative breast cancer (TNBC) relies largely on chemotherapies. However, it is frequent that TNBC patients develop resistance to the chemotherapy drugs. Generation of drug-resistant cell lines facilitates the identification of drug resistance. Here, we established two paclitaxel (PTX)-resistant TNBC cancer cell lines using an intermittent and stepwise method and found that long non-coding RNA long intergenic non-protein-coding RNA p53-induced transcript (LINC-PINT) was significantly decreased in PTX-resistant cancer cells. Ectopic expression of LINC-PINT sensitized both PTX-resistant TNBC and wild-type TNBC to PTX. Moreover, RNA immunoprecipitation showed that LINC-PINT bound to RNA-binding protein NONO. Overexpression of LINC-PINT resulted in the degradation of NONO in a proteasome-dependent manner and vice versa. Knockdown of NONO with siRNA sensitized TNBC to PTX. We further analyzed the expression level of LINC-PINT and NONO in patient samples via online database and found that LINC-PINT and NONO may function antagonistically in all types of breast cancers. Taken together, our data illustrated a tumor suppressor role of LINC-PINT in sensitizing TNBC to chemotherapies via destabilizing NONO.

Spatial-Resolution Cell Type Proteome Profiling of Cancer Tissue by Fully Integrated Proteomics Technology.

Increasing attention has been focused on cell type proteome profiling for understanding the heterogeneous multicellular microenvironment in tissue samples. However, current cell type proteome profiling methods need large amounts of starting materials which preclude their application to clinical tumor specimens with limited access. Here, by seamlessly combining laser capture microdissection and integrated proteomics sample preparation technology SISPROT, specific cell types in tumor samples could be precisely dissected with single cell resolution and processed for high-sensitivity proteome profiling. Sample loss and contamination due to the multiple transfer steps are significantly reduced by the full integration and noncontact design. H&E staining dyes which are necessary for cell type investigation could be selectively removed by the unique two-stage design of the spintip device. This easy-to-use proteome profiling technology achieved high sensitivity with the identification of more than 500 proteins from only 0.1 mm2 and 10 µm thickness colon cancer tissue section. The first cell type proteome profiling of four cell types from one colon tumor and surrounding normal tissue, including cancer cells, enterocytes, lymphocytes, and smooth muscle cells, was obtained. 5271, 4691, 4876, and 2140 protein groups were identified, respectively, from tissue section of only 5 mm2 and 10 µm thickness. Furthermore, spatially resolved proteome distribution profiles of enterocytes, lymphocytes, and smooth muscle cells on the same tissue slices and across four consecutive sections with micrometer distance were successfully achieved. This fully integrated proteomics technology, termed LCM-SISPROT, is therefore promising for spatial-resolution cell type proteome profiling of tumor microenvironment with a minute amount of clinical starting materials.

Tau expression correlated with breast cancer sensitivity to taxanes-based neoadjuvant chemotherapy.

The purpose of this study was to investigate the correlation between tau expression in primary breast cancer and sensitivity to taxanes during neoadjuvant chemotherapy in patients with breast cancer. We used immunohistochemistry to examine tau expression in breast cancer biopsies from 113 primary breast cancer patients and evaluated the correlation between tau expression and taxane sensitivity. Twenty-eight (24.78 %, 28/113) patients were positive for tau expression. After taxanes-based neoadjuvant chemotherapy, 40 patients achieved pathological complete response (pCR) (35.4 %). Among the 40 patients with pCR, five (12.5 %) were positive for tau expression. In univariate analysis, estrogen receptor (ER), progesterone receptor, human epidermal growth factor receptor 2 (HER2), and tau were found to be significantly predictive of a pCR (P = 0.001, 0.030, 0.002, and 0.025, respectively). Tau, ER, and HER2 status were significant for pCR on multivariate analysis (P = 0.025, 0.005, and 0.043, respectively). Tau expression was positively related to ER (P = 0.007) and progestin receptor (P = 0.008). In conclusion, tau protein expression correlated with breast cancer sensitivity to taxanes-based neoadjuvant chemotherapy; patients negative for tau expression were more likely to achieve pCR.

Value of UGT2B7-161 Single Nucleotide Polymorphism in Predicting the Risk of Cardiotoxicity in HER-2 Positive Breast Cancer Patients Who Underwent Pertuzumab Combined with Trastuzumab Therapy by PSL.

Objective: To explore the value of uridine diphosphate-glucuronosyltransferase 2B7 (UGT2B7)-161 single nucleotide polymorphism in predicting the occurrence of cardiotoxicity in Chinese human epidermal growth factor 2 (HER-2) positive breast cancer patients who underwent pertuzumab combined with trastuzumab Therapy. Methods: Fifty patients with HER-2 positive breast cancer who planned to receive trastuzumab and pertuzumab therapy for more than four cycles were enrolled in this study, and blood samples were collected. Thirty healthy volunteers of matching ages were selected as the control group. Myocardial parameters such as global work index, global effective work, and global wasted work were measured before treatment (M0) and at the end of four cycles of treatment month three (M3). Blood samples were collected from patients at the M0 stage, and polymorphisms of the UGT2B7-161 gene were detected to evaluate the predictive ability of different gene phenotypes on the myocardial drug toxicity injury. Results: There were 35 myocardial work decreased events among 50 patients. There were 24 (47.3%), 15 (40.8%), and 11 (11.8%) patients carrying UGT2B7-161 CC, CT, and TT genotypes, respectively. The occurrence of myocardial work decreased was decreased in UGT2B7-161 TT and CT genotypes (12.5%) compared with CC genotype (41.7%) with statistical significance (P < 0.001). Multivariate logistic regression model analysis exhibited that UGT2B7-161 genotypes, body mass index, and cardiac troponin I were independent factors influencing the risk of cardiotoxicity. Conclusion: UGT2B7-161 single nucleotide polymorphism is a potential predictive factor for cardiotoxicity in HER-2 positive breast cancer patients receiving trastuzumab and pertuzumab dual-targeted drug therapy.