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Long noncoding RNAs have an essential role in the tumorigenesis of breast cancer (BC). Nonetheless, the consequences of long intergenic noncoding RNA 00641 (LINC00641) in BC remain unidentified. This study shows that LINC00641 expression level was decreased in BC tissues. LINC00641 expression level was negatively related to tumor size, lymphnode metastasis, as well as clinical stage. LINC00641 overexpression inhibited cell proliferation, migration, and invasion but stimulated apoptosis in BC cells. LINC00641 overexpression also remarkably reduced BC growth and metastasis in vivo. LINC00641 acts as a competitive endogenous RNA to sponge miR-194-5p. miR-194-5p level was higher in BC tissues and cells compared with normal-adjacent tissues and normal breast epithelial cell. miR-194-5p expression was negatively correlated with LINC00641 expression in BC tissues. miR-194-5p overexpression reversed the effects of LINC00641 on cell proliferation, cycle, apoptosis, migration, as well as invasion. In conclusion, LINC00641 inhibits BC cell proliferation, migration, as well as invasion by sponging miR-194-5p. K E Y W O R D S breast cancer, LINC00641, lncRNA, metastasis, proliferation

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Background Long intergenic non-protein coding RNA00665 (LINC00665) plays a crucial tumorigenic role in many cancers, such as gastric cancer and lung adenocarcinoma. However, its role and mechanism of action in the progression of breast cancer (BC) are unknown. Methods LINC00665 expression levels were determined using quantitative polymerase chain reaction analysis with BC tissues and cell lines. BC cell proliferation was tested by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, whereas BC cell migration and invasion capabilities were analyzed by performing transwell migration assays. Percentages of apoptotic cells were measured by flow cytometry. Interactions between LINC00665 and miR-3169-5p were examined by performing luciferase reporter assays, and the expression levels of proteins, such as β-catenin, were examined by western blot analysis. Results LINC00665 was expressed at high levels in BC tissues and cells. Upregulated LINC00665 expression correlated with tumor size and tumor, node, and metastasis stages, but not with the age of patients. LINC00665 knockdown inhibited BC cell proliferation, migration, and invasion, whereas it promoted apoptosis. Moreover, bioinformatics analysis and the luciferase reporter assay revealed that LINC00665 bound the microRNA (miR) miR-3619-5p. miR-3619-5p expression correlated negatively with LINC00665 expression in BC tissues. miR-3619-5p overexpression inhibited BC cell proliferation, migration, and invasion, but promoted apoptosis. Simultaneous knockdown of LINC00665 and miR-3619-5p led to increased cell proliferation, migration, and invasion, and inhibited apoptosis. Additionally, catenin beta 1, which encodes the β-catenin protein, was the target gene of miR-3619-5p. β-catenin expression clearly decreased after LINC00665 knockdown and miR-3619-5p overexpression, but increased after simultaneous knockdown of LINC00665 and miR-3619-5p. Conclusion LINC00665 knockdown inhibited BC cell proliferation and invasion by binding miR-3619-5p and inhibiting β-catenin expression.

BackgroundAccurate survival prediction of triple-negative breast cancer (TNBC) is essential in the decision-making of adjuvant treatment. The aim of this prospective study was to develop a nomogram that predicts overall survival and assists adjuvant treatment formulation.MethodsA total of 16,977 patients with pT1-2N0M0 TNBC between 2010 and 2015 from the SEER database were enrolled. Independent prognostic factors associated with overall survival (OS) were identified using univariate and multivariate Cox regression hazards method and utilized to compose the nomogram. The survival benefit of adjuvant treatment on OS were analyzed after stratification by nomogram sum-score.ResultsPatients were randomized 7:3 into the training and validation cohorts. Multivariate analysis revealed that age at diagnosis, grade, tumor size, laterality, and mastectomy type were independent prognostic factors of OS and were integrated to develop a nomogram for predicting prognosis. Patients were stratified into 3 prognostic subgroups according to the sum-score of our nomogram. There were no significant differences found in OS between surgery alone and other adjuvant treatment strategies in low risk group. In moderate risk group, patients receiving chemotherapy or the combination of chemotherapy and radiotherapy showed better OS than those receiving surgery alone or radiotherapy alone. For patients in high risk group, the combination of chemotherapy and radiotherapy could maximally improve the overall survival rate of patients.ConclusionA novel nomogram for OS prediction and risk stratification in patients with pT1-2N0M0 TNBC was developed. This cohort study reveals the prognostic roles of different adjuvant treatment strategies in subgroups, which may provide a reference for the decision-making of postoperative treatment, eventually improving prognosis for individual patients.

Patients with Luminal A breast cancer often have favorable prognosis, but some of these patients still have lymph node metastases, it remains unclear what the role of adjuvant chemotherapy is in Luminal A subtype with lymph node metastases. The aim of this study was to find a new method to distinguish which Luminal A patient can be benefited from chemotherapy. We retrospectively investigated the inconsistency of molecular subtypes between primary foci and metastatic axillary lymph nodes in Luminal A breast cancer patients, and analyzed the clinicopathologic characteristics, Recurrence score (RS), disease-free survival (DFS), and overall survival (OS) in 146 Luminal A breast cancer patients. The discordance of molecular subtypes between primary foci and metastatic lymph nodes were explored by univariate and multivariate logistic regression. The DFS and OS were calculated by the Kaplan-Meier survival curves, and the Cox regression analyses were performed to identify independent prognostic factors for DFS and OS. In our results, the inconsistency was found in 55 patients (55/146, 37.67 %). Lymphatic vascular invasion (OR 6.402, 95 % CI 2.371-17.287, P < 0.001), lymph node stage (OR 2.147, 95 % CI 1.095-4.209, P = 0.026), and histological grade (OR 3.319, 95 % CI 1.101-8.951, P = 0.032) were significantly related to the inconsistency. The inconsistent group (non-Luminal A variations) had a poor prognosis compared with the consistent group, the DFS between the two groups was significantly different (P = 0.022), but the OS did not have obvious difference (P = 0.140). Moreover, the inconsistency was associated with high RS (P = 0.036). In conclusion, more aggressive molecular subtypes in metastatic lymph nodes, which associated with poor prognosis, were observed in Luminal A breast cancer patients, which indicate that chemotherapy is necessary for these patients.

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