School of Medicine and Health Sciences Poster Presentations

miR-200b may serve as therapeutic target for triple negative breast cancer

Document Type

Poster

Keywords

Breast cancer; miR-200b; triple-negative

Publication Date

Spring 2017

Abstract

Breast cancer progression involves stepwise transition from atypical ductal hyperplasia (ADH), to ductal carcinoma in situ (DCIS) and then to invasive ductal carcinoma (IDC). Among the IDCs, triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis, and accounts for a large number of metastatic cases and deaths. The dysregulation of microRNAs (miRNAs) in breast cancer has been widely reported. The stability of miRNAs in Formalin-Fixed, Paraffin-Embedded (FFPE) tissues and body fluids makes miRNAs as attractive diagnostic and therapeutic markers in breast cancer. The miR-200 family consisting of 5 members (miR-200a, -200b, -200c, -141, -429), has been shown to play crucial roles in cancer initiation and metastasis, and potentially be useful for the diagnosis and treatment of cancer. And miR-200 family has been shown to affect each step of the tumor metastatic cascade. Stable expression of miR-200b greatly reduced metastatic potential of TNBC cells, such as MDA-MB-231. However, the exact role of miR-200b in TNBCs is yet to be revealed. Our objective is to elucidate the potential diagnostic and therapeutic role of miR-200b in TNBC. In the present work, breast cancer cell lines were obtained from ATCC and cultured as instructed. With GW IRB approval, the breast cancer tissue blocks were obtained along with their pathological report, and subject to microdissection. The peripheral blood samples from patients were collected. Total RNA was isolated using Trizol reagent (Life Technologies) following the manufacturer’s instructions. Real-time qRT-PCR analysis was performed using Taqman MiRNA Reverse Transcript Kit (Applied Biosystem). The results were analyzed by the Student’s t-test. We found that lower expression of miR-200b in TNBC cells lines such as MDA-MB-231, Hs578T and MDA-MB-468, compared to non-TNBC cells lines, MCF-7, T47D and the immortalized epithelial cells line MCF-10A. In clinical sample analysis, we found that lower expression of miR-200b in 8 of 10 (80%) TNBCs while in 9 of 20 (45%) non-TNBC tissues. However, we did not detect any significant changes of miR-200b expression among ADH, DCIS and IDC in both tissue and blood samples. These results suggest that loss of miR-200b expression plays a crucial role in TNBC aggressiveness, and targeting miR-200b may be a novel approach in treating TNBC.

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Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Open Access

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Poster to be presented at GW Annual Research Days 2017.

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miR-200b may serve as therapeutic target for triple negative breast cancer

Breast cancer progression involves stepwise transition from atypical ductal hyperplasia (ADH), to ductal carcinoma in situ (DCIS) and then to invasive ductal carcinoma (IDC). Among the IDCs, triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis, and accounts for a large number of metastatic cases and deaths. The dysregulation of microRNAs (miRNAs) in breast cancer has been widely reported. The stability of miRNAs in Formalin-Fixed, Paraffin-Embedded (FFPE) tissues and body fluids makes miRNAs as attractive diagnostic and therapeutic markers in breast cancer. The miR-200 family consisting of 5 members (miR-200a, -200b, -200c, -141, -429), has been shown to play crucial roles in cancer initiation and metastasis, and potentially be useful for the diagnosis and treatment of cancer. And miR-200 family has been shown to affect each step of the tumor metastatic cascade. Stable expression of miR-200b greatly reduced metastatic potential of TNBC cells, such as MDA-MB-231. However, the exact role of miR-200b in TNBCs is yet to be revealed. Our objective is to elucidate the potential diagnostic and therapeutic role of miR-200b in TNBC. In the present work, breast cancer cell lines were obtained from ATCC and cultured as instructed. With GW IRB approval, the breast cancer tissue blocks were obtained along with their pathological report, and subject to microdissection. The peripheral blood samples from patients were collected. Total RNA was isolated using Trizol reagent (Life Technologies) following the manufacturer’s instructions. Real-time qRT-PCR analysis was performed using Taqman MiRNA Reverse Transcript Kit (Applied Biosystem). The results were analyzed by the Student’s t-test. We found that lower expression of miR-200b in TNBC cells lines such as MDA-MB-231, Hs578T and MDA-MB-468, compared to non-TNBC cells lines, MCF-7, T47D and the immortalized epithelial cells line MCF-10A. In clinical sample analysis, we found that lower expression of miR-200b in 8 of 10 (80%) TNBCs while in 9 of 20 (45%) non-TNBC tissues. However, we did not detect any significant changes of miR-200b expression among ADH, DCIS and IDC in both tissue and blood samples. These results suggest that loss of miR-200b expression plays a crucial role in TNBC aggressiveness, and targeting miR-200b may be a novel approach in treating TNBC.