Downregulation of microRNA‐15a‐3p is correlated with clinical outcome and negatively regulates cancer proliferation and migration in human osteosarcoma

Abstract

In this study, we investigated the expression, correlation to clinical outcomes and biological functions of microRNA-15a-3p (miR-15a-3p) in human osteosarcoma.MiR-15a-3p expressions in osteosarcoma cell lines and clinical tissues of osteosarcoma patients were measured by qPCR. Relevance of endogenous miR15a-3p to osteosarcoma patients' clinicopathological factors or overall survival was statistically analyzed. In addition, the independence of miR-15a-3p predicting cancer patients' overall survival was analyzed by Cox regression method. Furthermore, in osteosarcoma cell lines, Saos-2 and HOS cells, miR-15a-3p was overexpressed through stable lentiviral transduction. The functional regulations of miR-15a-3p overexpression on cancer ell proliferation and migration were then analyzed. MiR15a-3p was significantly downregulated in osteosarcoma cell lines and human osteosarcoma tumors. Downregulation of endogenous miR-15a-3p in osteosarcoma tumors was significantly associated with cancer patient's poor clinical outcomes and low survival rate. Also, endogenous miR-15a-3p was confirmed to be an independent biomarker for predicating cancer patients' survival. In Saos-2 and HOS cells, lentivirus-induced miR-15a-3p overexpression had significantly tumor suppressing functions, by inhibiting both proliferation and migration. Significant downregulation of miR-15a-3p in osteosarcoma may be an independent biomarker to predicting cancer patients' poor prognosis. Overexpression miR-15a-3p may be an efficient functional meaning to suppress osteosarcoma development.

Long non-coding RNA UCA1 exerts growth modulation by miR-15a in human thyroid cancer TPC-1 cells

“…miR-15a usually acts as anti-oncogene in kinds of cancers. Just as Shi et al reported that endogenous miR-15a-3p silence in osteosarcoma tumours is significantly ascribed to cancer patient's poor clinical outcomes and low survival rate [21]. Besides that, lncRNA LINC00473 is overexpressed in colorectal cancer.…”

Long noncoding RNA PWRN1 is lowly expressed in osteosarcoma and modulates cancer proliferation and migration by targeting hsa‐miR‐214‐5p

“…All experiments were independently carried out for biological triplicates or more repeats, and the data were presented as means +/− standard errors. Statistical analysis was conducted on a Windows‐based SPSS software (version 19.0, SPSS), and using the methods in our previous publication, 27 with the exception that one‐way ANOVA with post‐hoc test, not student's t ‐test, was used in this study. A P value less than .05 was considered statistically significant.…”

“…Quantitative real time-PCR (qPCR) was carried out using the methods in our previous publications with slight modification. [25][26][27] Briefly, total RNA was extracted from osteosarcoma cell lines or clinical samples using a Trizol kit (Takara, Japan) according to the manufacturer's protocol. Reverse transcription was conducted using a PrimeScript RT Master Mix (Takara, Japan).…”

“…Cell proliferation assay was carried out using the method in our previous publication. 27 Briefly, a Vybrant 3-[4,5dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) Cell Proliferation Assay (Invitrogen, USA) was conducted according to the manufacturer's protocol. Cancer cell proliferating rates were directly measured as absorbance at an optical density (O.D.)…”

Prognostic Value of MicroRNA-15a in Human Cancers: A Meta-Analysis and Bioinformatics

“…Downregulation of miRNA-15a has recently been reported in patients with CLL [7], non-small-cell lung cancer [10], prostate cancer [11], ovarian cancer [12], and hepatocellular carcinoma [13]. As an important member of miRNA-15/16 cluster, the influence of miRNA-15a on the prognosis of colorectal cancer [14–17], osteosarcoma [18], esophageal squamous cell carcinoma [19], glioma [20], breast cancer [21], cholangiocarcinoma [22], and multiple myeloma [23] has been reported. However, the results were insignificant or opposite.…”