Downregulation of miRNA‐141 in breast cancer cells is associated with cell migration and invasion: involvement of ANP32E targeting

Abstract

MicroRNAs (miRNAs) regulate many cellular activities, including cancer development, progression, and metastasis. Some miRNAs are involved in breast cancer (BC) migration and invasion, thus affect patients’ prognosis. Microarray analysis was performed to compare miRNA expression in BC tissues, and results confirmed by qPCR. BC cell migration and invasion were studied in vitro with MDA‐MB‐231 cells using microplate transwell assays. miRNA targeting was investigated using luciferase assays, qPCR, and Western blot analysis in cells with overexpression of miRNA mimics. Knockdown of miRNA targets was performed using target siRNA lentiviral infection. Results show that microRNA‐141 (miR‐141) was downregulated in breast cancer tumor tissues compared with matched surrounding tissues. Downregulation of miR‐141 expression correlated with tumor stage, lymph node involvement, and expressions of PCNA, Ki67, and HER2. Overexpression of miR‐141 inhibited BC cell proliferation, migration, and invasion in vitro. ANP32E gene was selected as one putative target for further studies based on results from in silico analysis. Results from a dual‐luciferase reporter system suggested ANP32E as a direct target of miR‐141. Overexpression of miR‐141 downregulated ANP32E expression at both mRNA and protein levels in BC cells. Knockdown of ANP32E inhibited BC cell proliferation, migration, and invasion in vitro, mimicking the effect of the overexpression of miR‐141. Our study revealed important roles miR‐141 plays in BC growth and metastasis. Moreover, for the first time, we identified ANP32E as one of the miR‐141 targets, and demonstrated its involvement in the regulation of cell proliferation, migration, and invasion.

circGNB1 Facilitates Triple-Negative Breast Cancer Progression by Regulating miR-141-5p-IGF1R Axis

“…By analyzing the miRNA microarray data derived from TCGA, we found that high expression of miR-141-5p was associated with better OS in TNBC patients 1 (Figure 3B). According to the reported research, downregulation of miR-141-5p was associated with progression and trastuzumab resistance in breast cancer (Finlay-Schultz et al, 2015;Li et al, 2017;Han et al, 2019). Detected by qPCR analysis, miR-141-5p was downregulated in TNBC cell lines compared to that in mammary epithelial cell lines (Supplementary Figure S2A).…”

“…According to the bioinformatic analysis and public database, miR-141-5p was predicted as the downstream of circGNB1 and low expression of miR-141-5p was associated with an improved overall survival clinical outcome. Downregulation of miR-141 contributes to the cancer cell growth, migration, trastuzumab resistance and stem cell expansion in breast cancer (Finlay-Schultz et al, 2015;Li et al, 2017;Han et al, 2019). IGF1R is a receptor binding insulin-like growth factor with a high affinity with tyrosine kinase activity, which is highly overexpressed in most malignant tissues and enhances cell survival (Pollak, 2008).…”

The emerging role of the long non-coding RNA HOTAIR in breast cancer development and treatment

“…This phenomenon is coordinated by several proteins and noncoding RNA molecules, partially through similar mechanisms in different malignancies (Table 1). Negative impact of hyperactivity of HOTAIR has been shown on regulation of miR-141 and miR-326 in glioma cells [56,57], as well as suppression of miR-141 in breast cancer cells [58]. Enforced transcription of HOTAIR could also promote proliferation, invasion and metastasis in gynaecological malignancies and breast cancer [59][60][61], through different mechanisms including up-regulation of BCL-W and sponging miR-206 [62].…”

miR‑202 acts as a potential tumor suppressor in breast cancer

“…These RNAs are regulatory molecules that modulate the expression of functional genes, play an important role in many biological processes, and are expressed in a tissue-and time-specific manner. miRNAs regulate gene expression at the post-transcriptional level mainly via completely complementary or partially complementary binding to the 3' UTR of the target gene, resulting in degradation or translational repression of the target gene (2)(3)(4). Studies have shown that a variety of miRNAs are involved in malignant transformation processes, such as malignant proliferation, metastasis and recurrence, and apoptosis inhibition.…”