MicroRNA-340 inhibits the migration, invasion, and metastasis of breast cancer cells by targeting Wnt pathway

Abstract

MicroRNAs (miRNAs) play a key role in tumor metastasis based on their capacity to regulate the expression of tumor-related genes. Over-expression of key genes such as c-MYC and CTNNB1 (encoding β-catenin) in Wnt/β-catenin-dependent and ROCK1 in Wnt/β-catenin-independent signaling pathways (Rho/Rho-associated kinase (ROCK) signaling pathway) has already been identified as the hallmarks of many tumors, and their role in breast cancer has also been investigated and confirmed. miR-340 characterization as an onco-suppressor miRNA has been previously reported. However, the mechanism by which it inhibits metastasis has not been completely elucidated. Quantitative real-time PCR (qPCR), Western blot, and luciferase assays were used to confirm the effect of miR-340 on the 3'-untranslated region (UTR) of the target genes. Lentiviral particles containing miR-340 were also used to evaluate the effect of miR-340 restoration on cell proliferation, migration, and invasion in vitro in the invasive MDA-MB-231 cell line. By applying bioinformatic approaches for the prediction of miRNAs targeting 3'-UTRs of CTNNB1, c-MYC, and ROCK1, we found out that miR-340 could dramatically down-regulate metastasis by targeting Wnt signaling in breast cancer cells. In the current study, analyzing miR-340 by reverse transcription quantitative PCR (RT-qPCR) in MDA-MB-231 showed that it was remarkably down-regulated in the metastatic breast cancer cell line. We found that restoration of miR-340 in the invasive breast cancer cell line, MDA-MB-231, suppresses the expression of the target genes' messenger RNA (mRNA) and protein and, as a result, inhibits tumor cell invasion and metastasis. Our findings highlight the ability of bioinformatic approaches to find miRNAs targeting specific genes. By bioinformatic analysis, we confirmed the important role of miR-340 as a pivotal regulator of breast cancer metastasis in targeting previously validated (ROCK1) and potentially novel genes, i.e., (CTNNB1 and c-MYC).

MicroRNA-340 promotes the tumor growth of human gastric cancer by inhibiting cyclin G2

“…Examination of the expression status, biological function and underlying mechanisms of specific miRNAs in gastric cancer can contribute to the identification of novel biomarkers and therapeutic targets in human gastric cancer. Previous studies have shown that miR-340 plays an important role in human cancers (8)(9)(10)(11)(12)(13)(14). It was found to inhibit the metastatic behavior of breast cancer cells (14) while it decreased the proliferation and promoted the cell apoptosis of prostate cancer cells (13,18).…”

“…MicroRNA-340 (miR-340) has been found to play a critical role in human cancers, including breast (8,9), prostate (10,11), and esophageal cancer (12), hepatocellular carcinoma (13) and glioma (14). Functionally, miR-340 was found to inhibit the migration and invasion of breast cancer cells by inhibiting the Wnt pathway (8).…”

“…Functionally, miR-340 was found to inhibit the migration and invasion of breast cancer cells by inhibiting the Wnt pathway (8). In prostate cancer, miR-340 was found to inhibit cell proliferation and promote cell apoptosis by inhibiting high-mobility group nucleosome-binding domain 5 (11).…”

Up-regulation of microRNA-340 promotes osteosarcoma cell apoptosis while suppressing proliferation, migration, and invasion by inactivating the CTNNB1-mediated Notch signaling pathway

“…Mohammadi-Yeganeh et al . [36] have reported increasing miR-340 in breast cancer led to significantly decreased expressions of its target genes; CTNNB1, ROCK1, and c-MYC by directly interacting with their 3′UTRs. Recently, Song et al [37] have also verified the target regulation relationship between miR-340 and CTNNB1 and identified that cells transfected with miR-340 mimics lowered CTNNB1 expression by targeting 3′UTR of CTNNB1 mRNA.…”

Hepatitis B virus promotes cancer cell migration by downregulating miR-340-5p expression to induce STAT3 overexpression

“…miRNAs are endogenous, evolutionarily conserved, small noncoding RNA molecules (18–25 nucleotides in length) that negatively regulate the expression of numerous target genes at the posttranscriptional level through sequence-dependent translational repression and/or target mRNA degradation [7]. Recent studies have revealed that miRNA-340 (miR-340) expression is downregulated in several types of cancer, demonstrating that miR-340 can act as a tumor suppressor and is, thus, involved in cell differentiation, proliferation, apoptosis, and tumor cell migration and invasion [8–11]. In addition, a previous study indicated that miR-340 represses the proliferation, migration, and invasion of HCC cells by targeting the Janus kinase (JAK) via the JAK1/signal transducer and activator of transcription (STAT)3 signaling pathway [12].…”