MiR‐127‐3p inhibits cell growth and invasiveness by targeting ITGA6 in human osteosarcoma

Abstract

Osteosarcoma (OS) is one of the most universal malignant bone tumors that occur mostly in children and adolescents. This study aimed to investigate the roles of miR-127-3p and integrin subunit-α 6 (ITGA6) in OS proliferation, apoptosis, invasion and migration, and to explore the possible molecular mechanism and target relationship. By conducting quantitative real-time polymerase chain reaction (qRT-PCR) and western blot, the microRNA (miRNA) and protein expressions of miR-127-3p and ITGA6 in both tissues and cells were determined. The expression of apoptosis and migration related were also detected by western blot. The target relationship between miR-127-3p and ITGA6 was predicted by TargetScan and verified by dual-luciferase reporter assay. The biological functions of miR-127-3p and ITGA6 in OS were investigated by following experiments: cell counting kit 8 (CCK-8) and colony formation assays to inspect cell proliferation, flow cytometry, and caspase 3 activity assay to examine apoptosis, and transwell and wound healing assays to analyze invasion and migration. Significant down-regulation of miR-127-3p and up-regulation of ITGA6 was found out in OS tissues and cells. ITGA6 was proved to be the downstream target gene of miR-127-3p and functioned as a tumor promotor in OS, while miR-127-3p restrained deterioration of OS by suppressing cell viability, reducing migration and invasion, and promoting apoptosis. MiR-127-3p suppressed proliferation, invasion, and migration while stimulated apoptosis of OS cells through knocking down ITGA6. © 2018 IUBMB Life, 70(5):411-419, 2018.

Tumor Suppressor Function of miR-127-3p and miR-376a-3p in Osteosarcoma Cells

“…Downregulation of miR-127 has been shown to be a common feature in several types of cancer, including ovarian cancer [27], gastric cancer [28], squamous cell carcinoma [26], pancreatic cancer [31], giant cell tumor of bone [35], and osteosarcoma [36]. Likewise, downregulation of miR-376a has…”

“…Downregulation of miR-127 has been shown to be a common feature in several types of cancer, including ovarian cancer [27], gastric cancer [28], squamous cell carcinoma [26], pancreatic cancer [31], giant cell tumor of bone [35], and osteosarcoma [36]. Likewise, downregulation of miR-376a has been reported in multiple cancer types, including breast cancer [32], lymphoma [30], non-small-cell lung cancer [29], giant cell tumor of bone [35], and osteosarcoma [37].…”

“…Since miRNAs represent highly attractive targets for the development of new therapeutic strategies, and tumor suppressor functions of miR-127 and miR-376a have already been demonstrated in osteosarcoma cell lines in vitro [36][37][38], we aimed to validate these tumor suppressor functions in further osteosarcoma cell lines and further to analyze the impact of candidate miRNA restoration on tumor engraftment and growth in vivo.…”

“…Therapeutic targeting of these candidate miRNAs would thus simultaneously influence multiple cancer-related pathways, potentiating the effectiveness of this therapy approach. Known miR-127 target genes include ITGA6 (integrin alpha-6) [36], SETD8 (lysine methyltransferase 8) [38], WNT7A (Wnt Family Member 7A) [28], BAG5 (BCL2-associated athanogene 5) [43], and COA1 (Cytochrome C Oxidase Assembly Factor 1 Homolog) [35]. ITGA6 has been shown to enhance tumor invasion and the activity of tumor-initiating cells in metastatic breast cancer [44].…”

LncRNA FOXD3-AS1 promoted chemo-resistance of NSCLC cells via directly acting on miR-127-3p/MDM2 axis

“…So far, the role of miR-127-3p has been uncovered in several types of malignant tumors. MiR-127-3p was down-regulated in osteosarcoma tissues and cell lines and acted as a tumor-suppressor in osteosarcoma [20,25]. The tumor suppressive effects of miR-127-3p was also uncovered in ovarian cancer [19].…”