A multicenter single-arm trial of neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2-positive breast cancer.

The objective of this multicenter, single-arm trial (ChiCTR1900022293) was to explore the efficacy and safety of neoadjuvant therapy with epirubicin, cyclophosphamide, and pyrotinib followed by docetaxel, trastuzumab, and pyrotinib (ECPy-THPy) in the treatment of patients with stage II-III HER2-positive breast cancer. The present study enrolled patients with stage II-III HER2-positive breast cancer. Epirubicin and cyclophosphamide were administrated for four 21-day cycles, followed by four cycles of docetaxel and trastuzumab. Pyrotinib was taken orally once per day throughout the treatment period. The primary endpoint was total pathological complete response (tpCR, ypT0/is ypN0) rate in the modified intention-to-treat (mITT) population. In total, 175 patients were included. The tpCR rate was 68.6% (95% CI, 60.7-75.8%), while the objective response rate was 89.1%. In the post-hoc subgroup analysis, no association between clinical characteristics and the tpCR rate was observed. The most common grade ≥3 adverse events were diarrhea (54.3%), followed by white blood cell count decreased (5.1%), and neutrophil count decreased (4.6%). In conclusion, the neoadjuvant regimen with ECPy-THPy showed promising pathological response and clinical benefits with an acceptable safety profile in patients with stage II-III HER2-positive breast cancer.

Peripheral blood inflammatory indexes in breast cancer: A review.

Immune and inflammatory responses play an important role in tumorigenesis and metastasis. Inflammation is an important component of the tumor microenvironment, and the changes in inflammatory cells may affect the occurrence and development of tumors. Complete blood count at the time of diagnosis and treatment can reflect the inflammatory status within the tumor. Studies have shown that the number of certain inflammatory cells in peripheral blood and their ratios are important prognostic factors for many malignancies, including neutrophil, lymphocyte, monocyte, and platelet counts, as well as neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, systemic immune-inflammation index, systemic inflammation response index and pan-immune-inflammation-value. The value of peripheral blood inflammation indexes in predicting the efficacy and prognosis of breast cancer neoadjuvant therapy is worth recognizing. This review details the application of peripheral blood inflammation indexes in the evaluation of efficacy and prediction of prognosis in neoadjuvant therapy for breast cancer, aiming to provide a more comprehensive reference for the comprehensive diagnosis and treatment of breast cancer.

JHDM1D-AS1-driven inhibition of miR-940 releases ARTN expression to induce breast carcinogenesis

Introduction As ceRNA network of long non-coding RNA (lncRNA)–microRNA (miR)–messenger RNAs (mRNA) can be predicted on the basis of bioinformatics tools, we are now one step closer to deeper understanding carcinogenic mechanisms. In this study, we clarified the mechanistic understanding of JHDM1D-AS1-miR-940-ARTN ceRNA network in the development of breast cancer (BC). Materials and Methods The lncRNA–miRNA–mRNA interaction of interest was predicted by in silico analysis and identified by conducting RNA immunoprecipitation, RNA pull-down and luciferase assays. The expression patterns of JHDM1D-AS1, miR-940 and ARTN in BC cells were altered by lentivirus infection and plasmid transfection for functional assays on the biological properties of BC cells. Finally, the tumorigenic and metastatic abilities of BC cells were assessed in vivo. Results JHDM1D-AS1 was highly expressed, while miR-940 was poorly expressed in BC tissues and cells. JHDM1D-AS1 could competitively bind to miR-940, whereby promoting the malignant behaviors of BC cells. Furthermore, ARTN was identified as a target gene of miR-940. Through targeting ARTN, miR-940 exerted a tumor-suppressive role. In vivo experiments further confirmed that JHDM1D-AS1 enhanced the tumorigenesis and metastasis through up-regulation of ARTN. Conclusions Taken together, our study demonstrated the involvement of ceRNA network JHDM1D-AS1-miR-940-ARTN in the progression of BC, which highlighted promising therapeutic targets for BC treatment (AU)

JHDM1D-AS1-driven inhibition of miR-940 releases ARTN expression to induce breast carcinogenesis.

INTRODUCTION: As ceRNA network of long non-coding RNA (lncRNA)-microRNA (miR)-messenger RNAs (mRNA) can be predicted on the basis of bioinformatics tools, we are now one step closer to deeper understanding carcinogenic mechanisms. In this study, we clarified the mechanistic understanding of JHDM1D-AS1-miR-940-ARTN ceRNA network in the development of breast cancer (BC). MATERIALS AND METHODS: The lncRNA-miRNA-mRNA interaction of interest was predicted by in silico analysis and identified by conducting RNA immunoprecipitation, RNA pull-down and luciferase assays. The expression patterns of JHDM1D-AS1, miR-940 and ARTN in BC cells were altered by lentivirus infection and plasmid transfection for functional assays on the biological properties of BC cells. Finally, the tumorigenic and metastatic abilities of BC cells were assessed in vivo. RESULTS: JHDM1D-AS1 was highly expressed, while miR-940 was poorly expressed in BC tissues and cells. JHDM1D-AS1 could competitively bind to miR-940, whereby promoting the malignant behaviors of BC cells. Furthermore, ARTN was identified as a target gene of miR-940. Through targeting ARTN, miR-940 exerted a tumor-suppressive role. In vivo experiments further confirmed that JHDM1D-AS1 enhanced the tumorigenesis and metastasis through up-regulation of ARTN. CONCLUSIONS: Taken together, our study demonstrated the involvement of ceRNA network JHDM1D-AS1-miR-940-ARTN in the progression of BC, which highlighted promising therapeutic targets for BC treatment.

The HIF-1/SNHG1/miR-199a-3p/TFAM axis explains tumor angiogenesis and metastasis under hypoxic conditions in breast cancer.

Activation of hypoxia-inducible factors (HIFs) as a result of intratumoral hypoxia modulates a cascade of molecular pathways thus leading to angiogenesis and metastasis in many solid tumors, including breast cancer (BC). In our paper, we report a regulatory axis of HIF-1, SNHG1, miR-199a-3p, and mitochondrial transcription factor A (TFAM) involved in tumor angiogenesis and metastasis under hypoxic conditions in BC. The expression of SNHG1 was determined in human BC cells cultured in hypoxia (1% O2 , 24 h) and normoxia (20% O2 , 24 h). Cultured MDA-MB-231 cells were assayed for the proliferation, migration, invasion, angiogenesis in vitro by using EdU staining, transwell chamber assays, Matrigel-based angiogenesis assays, tumorigenesis, and lung metastasis in vivo by using an orthotopic-transplant model of human BC. Dual-luciferase reporter assay, chromatin immunoprecipitation quantitative polymerase chain reaction assay, fluorescence in situ hybridization assay, RNA-binding protein immunoprecipitation assay, and RNA pull-down were performed to test interaction between HIF-1 and SNHG1, SNHG1 and miR-199a-3p, miR-199a-3p and TFAM. SNHG1 was increased under hypoxic conditions at a HIF-1-dependent manner. SNHG1 knockdown tempered MDA-MB-231 cell proliferation, migration, invasion, angiogenesis, in vitro, tumorigenesis, and lung metastasis in vitro. SNHG1 was co-expressed with miR-199a-3p and regulated the TFAM, a target gene of miR-199a-3p. SNHG1 increased the TFAM by binding with miR-199a-3p, thus promoting BC development and metastasis. These results support a regulatory axis consisting of HIF-1, SNHG1, miR-199a-3p, and TFAM during BC development and metastasis under hypoxic conditions, providing an opportunity to develop targeted therapeutics for BC.

LINC00096 Promotes the Proliferation and Invasion by Sponging miR-383-5p and Regulating RBM3 Expression in Triple-Negative Breast Cancer.

BACKGROUND: Recent studies revealed that long non-coding RNAs (lncRNA) play crucial roles in cancer initiation and progression. However, the function and underlying mechanism of lncRNAs in triple-negative breast cancer (TNBC) are little investigated. METHODS: qRT-PCR was used to investigate LINC00096 expression in TNBC tissues and cells. Function assays were used to test the effects of LINC00096 on TNBC cells progression. In addition, luciferase reporter and qRT-PCR assays were used to determine the underlying mechanism of LINC00096 on TNBC progression. RESULTS: In our present study, we identify LINC00096 as one of the most upregulated lncRNA in TNBC progression by using microarray screening. High LINC00096 expression was obviously related to advanced tumor stage, metastasis, poor prognosis of patients. Loss-of-function assays showed that LINC00096 suppression reduced TNBC cells proliferation and invasive abilities in vitro. Mechanistically, we demonstrated that LINC00096 directly interacted with miR-383-5p, subsequently acted as a miRNA sponge to increase RBM3 expression. CONCLUSION: In the present study, we indicated that LINC00096 might promote the proliferation and invasion through regulating the miR-383-5p/RBM3 pathway in TNBC, which providing a novel therapeutic target for cancer treatment.

Retracted Article: Down-regulation of Rab10 inhibits hypoxia-induced invasion and EMT in thyroid cancer cells by targeting HIF-1α through the PI3K/Akt pathway.

Rab10, a member of the Rab family, is localized to endocytic compartments and serves as a regulator of intracellular vesicle trafficking. Previous studies mainly paid attention to the role of Rab10 in transport. Recently, Rab10 has been reported to be involved in the progression of various cancers. However, the biological functions of Rab10 in thyroid cancer remain unknown. In this study, we demonstrated that Rab10 was highly expressed in thyroid cancer tissues and cell lines. Down-regulation of Rab10 inhibited hypoxia-induced migration, invasion and epithelial-mesenchymal transition (EMT) of thyroid cancer cells. Moreover, HIF-1α and the PI3K/Akt pathway were involved in the inhibitory effect of Rab10 down-regulation on thyroid cancer cell invasion and EMT induced by hypoxia. Taken together, our study provided further evidence to support the role of Rab10 as a therapeutic target for thyroid cancer.

Knockdown of TRIM44 inhibits the proliferation and invasion in papillary thyroid cancer cells through suppressing the Wnt/ß-catenin signaling pathway.

Tripartite motif 44 (TRIM44), a member of the TRIM family, functions as a critical regulator in several types of malignancy. However, the role of TRIM44 in thyroid cancer has never been revealed. Thus, in this study, to explore its role in PTC, we detected its expression patterns in human papillary thyroid cancer (PTC) tissues and cell lines, and investigated its effects on cell proliferation and invasion. Our results demonstrated that TRIM44 was highly expressed in human PTC tissues and cell lines. In addition, silencing of TRIM44 significantly suppressed the proliferation, migration/invasion, and the epithelial-mesenchymal transition (EMT) process in PTC cells. Furthermore, silencing of TRIM44 dramatically down-regulated the expression of ß-catenin, cyclin-D1 and c-Myc in PEC cells, and the activator of the Wnt/ß-catenin pathway LiCl rescued the anticancer effect of knockdown TRIM44 expression in PTC cells. In conclusion, this study reported here provided evidence that TRIM44 functions as an oncogene in PTC. Silencing of TRIM44 inhibits the proliferation, migration and invasion of PTC cells in part through suppression of the Wnt/ß-catenin signaling pathway. Thus, TRIM44 may be a potential therapeutic target for the treatment of PTC.

Long non-coding RNA MALAT1 promotes proliferation and invasion via targeting miR-129-5p in triple-negative breast cancer.

BACKGROUND: Long non-coding RNA Metastasis associated lung adenocarcinoma transcript 1(lncRNA MALAT1) play important roles in tumor progression. In the present study, we determined the regulatory function of MALAT1 in triple-negative breast cancer (TNBC). METHODS: A total of 43 cases of TNBC tissues and paired adjacent non-tumor tissues were collected for the research. MALAT1 expression was explored by qRT-PCR. In vitro functional validation experiments were used to determine the effect of MALAT1 on TNBC progression. We further identified the downstream target miRNAs for MALAT1. RESULTS: Relative expression of MALAT1 was increased in TNBC tissues and cell lines. High MALAT1 expression was closely correlated to advance clinical features and poor overall survival in TNBC patients. Function assay showed that MALAT1 silencing significantly decreased cell proliferation, migration, and invasion. Flow cytometry assay revealed that MALAT1 inhibition significantly induced cell cycle arrest in the G0/G1 phase. In addition, we showed that the roles of MALAT1 on TNBC cells progression was mediated by miR-129-5p. CONCLUSION: Our results demonstrated that the "MALAT1-miR-129-5p" axis might play an important role in the progression of TNBC, thereby might provide a potential therapeutic strategy for the treatment of TNBC.

A new bound on the block restricted isometry constant in compressed sensing.

This paper focuses on the sufficient condition of block sparse recovery with the [Formula: see text]-minimization. We show that if the measurement matrix satisfies the block restricted isometry property with [Formula: see text], then every block s-sparse signal can be exactly recovered via the [Formula: see text]-minimization approach in the noiseless case and is stably recovered in the noisy measurement case. The result improves the bound on the block restricted isometry constant [Formula: see text] of Lin and Li (Acta Math. Sin. Engl. Ser. 29(7):1401-1412, 2013).

Knockdown of PEBP4 suppresses proliferation, migration and invasion of human breast cancer cells.

Phosphatidylethanolamine-binding protein 4 (PEBP4), a member of the PEBP family, plays a pivotal role in tumor progression. However, the roles of PEBP4 in breast cancer remain unclear. Therefore, in the present study, we investigated the effects of PEBP4 on breast cancer cell proliferation, migration and invasion, and the underlying mechanism was also explored. Our results showed that the expression of PEBP4 was significantly up-regulated in breast cancer cell lines. Knockdown of PEBP4 inhibited breast cancer cell proliferation in vitro and tumor growth in vivo. Furthermore, knockdown of PEBP4 suppressed breast cancer cell migration and invasion with prevented EMT. Mechanistically, knockdown of PEBP4 inhibited breast cancer cell proliferation and migration through the inactivation of PI3K/Akt signaling pathway. In conclusion, the present study demonstrated for the first time that knockdown of PEBP4 inhibited the proliferation, invasion and tumorigenesis in breast cancer cells. Thus, PEBP4 may serve as a potential therapeutic target for the treatment of breast cancer.