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Zheng Y.,Tianjin Medical University | Zheng Y.,Key Laboratory of Cancer Prevention and Therapy | Zheng Y.,State Key Laboratory of Breast Cancer Research | Li S.,Tianjin Medical University | And 34 more authors.
Journal of Cancer | Year: 2015

There is an unmet clinical need to identify biomarkers for breast cancer neoadjuvant chemotherapy. Here, using miRNA TaqMan Low-Density Arrays (TLDA), we analyzed the miRNA expression profile in pre-treatment needle aspiration tumor samples from patients who received taxane-anthracycline-based neoadjuvant chemotherapy. Although, in an unsupervised hierarchical cluster analysis, the total miRNA expression profile could not generate a tree with clear distinction between pathologic complete response (pCR) and non-pCR classes, we found that elevated expression of miR-125b and miR-141 was associated with non-pCR. In vitro experiments indicated that inhibition of miR-125b and miR-141 expression reduced cellular survival in response to taxane-anthracycline treatment. Furthermore, co-transfection with miR-125b and miR-141 mimics increased resistance of MCF7 and BT549 cells to taxane-anthracycline induced cytotoxicity. Pathway analyses indicated that many of the target proteins of miR-125b are involved in apoptotic pathways and cell cycle control. Together, we provide evidence that elevated miR-125b and 141 expression predicts a poor clinical responsiveness of taxane-anthracycline-based neoadjuvant chemotherapy. © 2015 Ivyspring International Publisher.


Li S.,Tianjin Medical University | Li S.,Key Laboratory of Cancer Prevention and Therapy | Li S.,State Key Laboratory of Breast Cancer Research | Yang C.,Tianjin Medical University | And 21 more authors.
Breast Cancer Research and Treatment | Year: 2012

Invasive micropapillary carcinoma (IMPC) is an uncommon histological type of breast cancer. IMPC has a special growth pattern and a more aggressive behavior than invasive ductal carcinomas of no special types (IDC-NSTs). microRNAs are a large class of non-coding RNAs involved in the regulation of various biological processes. Here, we analyzed the small RNA transcriptomes of five formalin-fixed paraffin-embedded (FFPE) pure IMPC samples and five FFPE IDC-NSTs samples by means of next-generation sequencing, generating a total of >170,000,000 clean reads. In an unsupervised cluster analysis, differently expressed miRNAs generated a tree with clear distinction between IMPC and IDC-NSTs classes. Paired fresh-frozen and FFPE specimens showed very similar miRNA expression profiles. By means of RT-qPCR, we further investigated miRNA expression in more IMPC (n = 22) and IDC-NSTs (n = 24) FFPE samples and found let-7b, miR-30c, miR-148a, miR-181a, miR-181a*, and miR-181b were significantly differently expressed between the two groups. We also elucidated several features of miRNA in these breast cancer tissues including 5′ variability, miRNA editing, and 3′ untemplated addition. Our findings will lead to further understanding of the invasive potency of IMPC and gain an insight into the diversity and complexity of small RNA molecules in breast cancer tissues. © 2012 Springer Science+Business Media, LLC.


Zhai L.,Tianjin Medical University | Zhai L.,State Key Laboratory of Breast Cancer Research | Li S.,Tianjin Medical University | Li S.,State Key Laboratory of Breast Cancer Research | And 13 more authors.
Pathology Research and Practice | Year: 2015

It has been reported that expression levels of DNA repair genes are frequently associated with chemotherapy sensitivity and prognosis in breast cancer (BC) subtypes. The poly (ADP-ribose) polymerase-1 (PARP1), one of the major DNA single-strand break (SSBs) repair proteins, has been demonstrated a role in BC development. Because many of the chemotherapeutic agents target the tumor cell DNA, a DNA damage repair protein function is expected to impact therapeutic responses. However, the predictive effect of PARP1 in neoadjuvant chemotherapy (NC) treated BC is still controversial. To investigate whether PARP1 expression in BC is a possible biomarker to predict chemotherapeutic response, we assessed PARP1 expression in BC specimens based on collagen gel droplet embedded culture-drug sensitivity test (CD-DST) (. in vitro) results and chemotherapeutic response of NC (. in vivo). The surgical specimens from 108 patients with BC were recruited for CD-DST and PARP1 immunohistochemistry. We found that higher nuclear PARP1 (nPARP1) expression correlated with increased in vitro chemosensitivity against docetaxel (. p=. 0.001) and epirubicin (. p=. 0.022) based on CD-DST results. We also found that tumors with high nPARP1 expression were more sensitive to anthracycline/taxane based chemotherapy and associated with pathologic responses to NC using univariate and multivariate analyses (. p=. 0.019 and p=. 0.037, respectively). Taken together, we conclude that nuclear expression of PARP1 is a useful marker to predict BC therapeutic responses. © 2014 Elsevier GmbH.


Li S.,Tianjin Medical University | Li S.,Key Laboratory of Cancer Prevention and Therapy | Li S.,State Key Laboratory of Breast Cancer Research | Meng H.,Tianjin Medical University | And 29 more authors.
Pathology Research and Practice | Year: 2013

Ductal carcinoma in situ (DCIS) is the most common type of non-invasive breast cancer. The currently accepted step-wise model suggests that breast cancer progressed in the following manner: normal breast cell → usually ductal hyperplasia (UDH) → atypical ductal hyperplasia (ADH) → DCIS → invasive ductal carcinoma (IDC). Therefore, DCIS can serve as a good model to analyze the mechanism underlying invasive breast cancer occurrence. MicroRNAs (miRNAs) are a novel class of small non-coding RNAs (~22. nt) involved in the regulation of various biological processes. Altered miRNA expression could also contribute to the origination of cancer, including breast cancer. Here, by using miRNA microarray and real time PCR, we analyzed the miRNA expression profile in 21 DCIS and the corresponding normal tissues. miR-10b, miR-125b, miR-132, miR-145, miR-154-3p, miR-382-5p and miR-409-3p were found to be significantly deregulated in DCIS. Results from CCK-8 assay showed that the overexpression of miR-132 could inhibit the proliferation of breast cancer cell line. High expression of miR-132 could also inhibit the colony formation. Our findings will lead to further understanding of the development of breast cancer. © 2012 Elsevier GmbH.

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