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MiRNA?490?3p promotes the metastatic progression of invasive ductal carcinoma.

ABSTRACT: MicroRNA (miRNA/mir)?490?3p has been defined as a tumor suppressor in different types of cancer, including breast cancer. However, miR?490?3p has been shown to function as a tumor suppressor and promoter in a context?dependent manner in hepatocellular and lung cancer. Contrary to previous studies, the present study revealed that miR?490?3p expression was significantly higher in invasive ductal carcinoma (IDC) tissue specimens, the most common form of breast cancer, compared to tumor?adjacent normal tissue specimens (n=20). Its expression was also higher in the more metastatic breast cancer cell line, MDA?MB?231, compared to the non?metastatic breast cancer cell line, MCF7, and the moderately metastatic breast cancer cell line, MDA?MB?468. The expression of miR?490?3p was induced following transforming growth factor (TGF)???induced epithelial?to?mesenchymal transition (EMT) in MCF10A cells. Gain?and loss?of?function assays revealed that the expression of miR?490?3p regulated the proliferation, colony formation, EMT, migration and invasion in vitro, but not the apoptosis of MDA?MB?468 and MDA?MB?231 cells. The knockdown of miR?490?3p expression in MDA?MB?231 cells inhibited experimental metastasis in a tumor xenograft assay. As in lung cancer, miR?490?3p was found to target and downregulate the expression of the tumor suppressor RNA binding protein poly r(C) binding protein 1 (PCBP1). PCBP1 protein and miR?490?3p expression inversely correlated in patients with ductal carcinoma in situ (DCIS; n=10; no nodal involvement) and IDC (n=10; different stages of metastatic progression) with a significantly higher miR?490?3p expression in patients with IDC compared to those with DCIS. The expression of miR?490?3p was negatively associated with both overall and disease?free survival in the patients with breast cancer included in the present study. On the whole, the results confirm a pro?metastatic role of miR?490?3p in IDC, establishing it as a biomarker for disease progression in these patients.

SUBMITTER: Lu N

PROVIDER: S-EPMC7757091 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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miRNA‑490‑3p promotes the metastatic progression of invasive ductal carcinoma.

Lu Ning N Zhang Mei M Lu Lu L Liu Yan-Zhao YZ Zhang Hai-Hong HH Liu Xiao-Dong XD

Oncology reports 20201202 2

MicroRNA (miRNA/mir)‑490‑3p has been defined as a tumor suppressor in different types of cancer, including breast cancer. However, miR‑490‑3p has been shown to function as a tumor suppressor and promoter in a context‑dependent manner in hepatocellular and lung cancer. Contrary to previous studies, the present study revealed that miR‑490‑3p expression was significantly higher in invasive ductal carcinoma (IDC) tissue specimens, the most common form of breast cancer, compared to tumor‑adjacent nor ...[more]

PMID: 33416185

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Project description:To obtain insight into the molecular basis of ductal carcinoma in situ (DCIS) and its progression by infiltrating surrounding tissue, we have performed cellular-based gene expression analysis of pure DCIS and DCIS with co-existing invasive ductal carcinoma (IDC) and compared the histological and molecular aspects between these morphologically identical lesions seeking to find key genes involved in DCIS progression. For that, 30 samples were evaluated, 4 non-neoplastic (N), 5 pure DCIS, 11 DCIS with co-existing IDC (DCIS-IDC) and 10 IDC. All samples were laser capture microdissected and RNAs were amplified using T7-based methodology. Microarray technology was performed using a customized cDNA platform containing 4,608 human genes. To classify the 4 sample groups according to molecular similarity we performed comparisons of their general expression pattern using ANOVA test (pFDR<0,01) followed by Tukey´s test (fold>l2l). Among the 4 sample groups, as expected, non-neoplastic cells reported the most distinct gene expression pattern. However, among the 3 groups of neoplastic cells, in contrast to morphological aspects, pure DCIS had the most distinct expression profile when compared to the other lesions: DCIS-IDC and IDC. Additionally, by comparison among pure DCIS, DCIS-IDC and N, we identified 147 genes potentially involved in DCIS progression. Unsupervised hierarchical cluster based on expression profile of this gene-set could discriminate DCIS-IDC from 60% of pure DCIS samples. Keywords: disease state analysis Fresh-frozen human breast samples were retrieved from the Tumor Tissue Biobank of the Medical and Research Center - Hospital A. C. Camargo, São Paulo. This research was approved by Ethic Committee of the Medical and Research Center - Hospital A. C. Camargo under number 587/04 and a written informed consent signed by all participants. All patients had presented at least 5 years of follow-up. Thirty samples were evaluated, 4 non-neoplastic breast samples (MN), 5 pure DCIS (stage 0; DCIS-0), 11 DCIS with co-existing IDC (DCIS) and 10 IDC. The non-neoplastic samples were obtained from perilesional mammary specimens from patients submitted to resection of benign lesions. All cells types were laser capture microdissected using PixCell II LCM system (Arcturus Engineering, Mountain View, CA). The total RNA was extracted by using the PicoPureä RNA Isolation kit (Arcturus Engineering # KT0204). A two-round linear amplification procedure based on T7-driven amplification was carried out. Amplified RNA was then used in a transcriptase reverse reaction into cDNA in the presence of Cy3- or Cy5-labeled dCTP. HB4a normal luminal epithelial mammary cell line (O’Hare et al 1991) was amplified following the same protocol and used as reference for microarray hybridizations. Dye swap was performed for each sample analyzed and used as replicate samples. For the raw_data (lowess_data), see Web Link below.

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MiRNA?490?3p promotes the metastatic progression of invasive ductal carcinoma.

Publications

miRNA‑490‑3p promotes the metastatic progression of invasive ductal carcinoma.

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