MicroRNA‐23a inhibits melanoma cell proliferation, migration, and invasion in mice through a negative feedback regulation of sdcbp and the MAPK/ERK signaling pathway

Abstract

Melanoma is the main cause of death associated with skin cancer. Surgical resection and adjuvant therapy are currently effective treatments, but the recurrence rate is very high. The understanding of microRNA (miR) dynamics after surgical resection of melanoma is essential to accurately explain the changes in the recurrence of melanoma. In this study, we hypothesized that microRNA‐23a (miR‐23a) affects the cell proliferation, migration, and invasion of melanoma with a mechanism related to SDCBP and the MAPK/ERK signaling pathway. To validate this, we performed a series of experiments in cells of melanoma modeled. Initially, positive expression of SDCBP and morphology of normal and melanoma tissues and cells were observed. Expression of miR‐23a, SDCBP, and MAPK/ERK signaling pathway‐related genes was identified in melanoma tissues. Melanoma cells transfected with mimic or inhibitor of miR‐23a or si‐SDCBP were detected to validate effect of miR‐23a on SDCBP and the MAPK/ERK signaling pathway. MTT assay, scratch test, transwell assay, and flow cytometry were performed to evaluate cell viability, invasion, metastasis, and apoptosis in vitro, respectively. Tumorigenicity assay in nude mice was conducted to test the tumorigenesis of the transfected cells in vivo. High positive expression of SDCBP and abnormal morphology were observed in melanoma tissues and cells. Reduced expression of miR‐23a and increased expression of SDCBP and MAPK/ERK signaling pathway‐related genes were identified in the melanoma tissues of melanoma mice. Overexpressed miR‐23a dampened SDCBP and the MAPK/ERK signaling pathway. The melanoma cells with overexpressed miR‐23a presented ascended cell apoptosis and descended cell proliferation, migration, invasion as well as tumor size. Taken together, our study demonstrated that miR‐23a could inhibit the development of melanoma in mice through a negative feedback regulation of SDCBP and the MAPK/ERK signaling pathway. © 2018 IUBMB Life, 71(5):587–600, 2019

Downregulation of SDCBP inhibits cell proliferation and induces apoptosis by regulating PI3K/AKT/mTOR pathway in gastric carcinoma

“…Recently, more and more studies have reported that the high expression of SDCBP is determined in various malignancies such as breast cancer [9], prostate cancer [10], melanoma cell [11], and glioma [12]. In the present study, our results showed that SDCBP acted as an oncogenic role in the development of GC.…”

“…such as breast cancer [9], prostate cancer [10], melanoma cell [11], and glioma [12]. In the present study, our results showed that SDCBP acted as an oncogenic role in the development of GC.…”

Exosomal miRNAs in tumor microenvironment

“…Exosomal miRNAs secreted by tumor cells have been reported to promote angiogenesis in TME. In nasopharyngeal carcinoma (NPC), exosomal miR-23a mediates angiogenesis by repressing TSGA10 and phosphorylation of ERK, which enhances tube generation ability of human umbilical vein endothelial cells (HUVECs) in vitro and in vivo [121,122]. Glioma stem cell-derived exosomal miR-21 stimulates VEGF/p-FLK/ VEGFR2 signaling pathway to promote angiogenesis in endothelial cells [123,124].…”

MicroRNA‑23a acts as an oncogene in pancreatic carcinoma by targeting TFPI‑2

“…For example, several studies have reported that miR-23a promoted the progression of a variety of cancers, including gastric cancer, colorectal and liver carcinoma ( 33-35 ). By contrast, miR-23a was found to serve as a cancer suppressor in melanoma and osteosarcoma, as the overexpression of miR-23a inhibited osteosarcoma cell proliferation, migration and invasive ability ( 36 ), and suppressed melanoma cell proliferation, migration and invasion in mice ( 37 ). The results of the current study revealed that miR-23a mRNA expression level was upregulated in PC cell lines (MiaPaCa2, Panc-1 and Aspc-1) compared with that in a normal pancreatic ductal cell line (hTERT-HPNE), suggesting that miR-23a may be associated with the tumorigenesis and progression of PC.…”