MicroRNA-543 suppresses colorectal cancer growth and metastasis by targeting KRAS, MTA1 and HMGA2

Abstract

miR-543 has been implicated as having a critical role in the development of breast cancer, endometrial cancer and hepatocellular carcinoma. However, the exact clinical significance and biological functions of miR-543 in colorectal cancer (CRC) remain unclear. Here, we found that miR-543 expression significantly downregulated in tumors from patients with CRC, APCMin mice and a mouse model of colitis-associated colon cancer. miR-543 level was inversely correlated with the metastatic status of patients with CRC and the metastatic potential of CRC cell lines. Moreover, ectopic expression of miR-543 inhibited the proliferation and metastasis of CRC cells in vitro and in vivo by targeting KRAS, MTA1 and HMGA2. Conversely, miR-543 knockdown promoted the proliferation, migration and invasion of CRC cells in vitro and augmented tumor growth and metastasis in vivo. Furthermore, we found that miR-543 expression was negatively correlated with the levels of KRAS, MTA1 and HMGA2 in clinical samples. Collectively, these data show that miR-543 inhibits the proliferation and metastasis of CRC cells by targeting KRAS, MTA1 and HMGA2. Our study highlights a pivotal role for miR-543 as a suppressor in the regulation of CRC growth and metastasis and suggests that miR-543 may serve as a novel diagnostic and prognostic biomarker for CRC metastasis.

MiR-543 Promotes Migration, Invasion and Epithelial-Mesenchymal Transition of Esophageal Cancer Cells by Targeting Phospholipase A2 Group IVA

“…Increasing numbers of studies have indicated that among numerous other miRNAs, miR-543 is also involved in the processes of initiation and maintenance of many kinds of cancers, including ESCC [17]. It has also been reported that miR-543 is down-regulated in breast cancer [19] and endometrial cancer [20] but functions as an oncogene in hepatocellular carcinoma [10,21]. These different conclusions may be caused by differences in the etiology and pathogenesis of these cancers.…”

“…Although these two types of miRNAs lead to different results, they both play decisive roles in various aspects of the progression of carcinogenesis, including invasion and migration [3,9]. Previous studies on miR-543 showed that it exerts an inhibitive influence in several cancers such as breast cancer and endometrial cancer, while in malignant hepatoma, it acts as a tumorigenesis promoter [10,11]. The miR-543 cluster is in the DLK1-DIO3 region on human chromosome 14.…”

MiR-543 Promotes Proliferation and Epithelial-Mesenchymal Transition in Prostate Cancer via Targeting RKIP

“…It has been reported that miR-543 promotes cell proliferation and metastasis in hepatocellular carcinoma, while it inhibited EMT through decreasing TWIST1 signaling in colorectal cancer [27, 34]. Furthermore, a recent study has also reported that miR-543 suppressed tumor growth and metastasis in colorectal cancer by targeting KRAS, MAT1 and HMGA2 [35]. However, the biological function and clinical significance of miR-543 in prostate cancer remains unclear.…”

Peripheral lung adenocarcinomas harboring epithelial growth factor receptor mutations with microRNA‑135b overexpression are more likely to invade visceral pleura

“…For example, miR-483-5p promotes the epithelial-mesenchymal transition (EMT), which is frequently accompanied by the invasive, metastatic transformation of lung adenocarcinoma cells (26). miR-543 inhibits the proliferation and metastasis of colorectal cancer (CRC) cells, which indicates that it may serve as a favorable diagnostic and biomarker for CRC metastasis (27). However, the potential to use molecules similar to these for cancer diagnosis has not yet been systematically explored.…”