Down-regulation of HCP5 inhibits cell proliferation, migration, and invasion through regulating EPHA7 by competitively binding miR-101 in osteosarcoma

Abstract

Patients with osteosarcoma (OS) usually have poor overall survival because of frequent metastasis. Long non-coding RNAs (lncRNAs) have been reported to be associated with tumorigenesis and metastasis. In this study, we investigated the expression and roles of lncRNA human histocompatibility leukocyte antigen (HLA) complex P5 (HCP5) in OS, aiming to provide a novel molecular mechanism for OS. HCP5 was up-regulated both in OS tissues and cell lines and high expression of HCP5 was associated to low survival in OS patients. Down-regulation of HCP5 inhibited cell proliferation, migration, and invasion, suggesting its carcinogenic role in OS. miR-101 was targeted by HCP5 and its expression was decreased in OS. The inhibitor of miR-101 reversed the impact of HCP5 down-regulation on cell proliferation, apoptosis, and metastasis in OS. Ephrin receptor 7 (EPHA7) was proved to be a target of miR-101 and had ability to recover the effects of miR-101 inhibitor in OS. In conclusion, lncRNA HCP5 knockdown suppressed cell proliferation, migration, and invasion, and induced apoptosis through depleting the expression of EPHA7 by binding to miR-101, providing a potential therapeutic strategy of HCP5 in OS.

LncRNA HCP5 as a potential therapeutic target and prognostic biomarker for various cancers: a meta‑analysis and bioinformatics analysis

“…After checking the full text of remaining articles, 28 studies were further excluded due to the reason of these studies without comparing the prognosis between high and low HCP5 expression or providing insufficient data for estimation of HR and 95% CI for survival rate or data from biographical analysis. Finally, nine literatures [ 13 , 15 – 20 , 26 , 27 ] coincided with the inclusion criteria were included in the present meta-analysis.

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“…The types of cancer in these studies included: non-small cell lung cancer, colorectal cancer, oral squamous cell carcinoma, clear cell renal cell carcinoma, gastric cancer, skin cutaneous melanoma and osteosarcoma. All included studies [ 13 , 15 – 20 , 26 , 27 ] evaluated the association between HCP5 expression levels and overall survival, the follow-up months ranged from 36 to 105. Five studies [ 13 , 15 , 16 , 19 , 26 ] reported the clinicopathological parameters.…”

“…There were nine studies evaluated the association between HCP5 expression levels and OS in this meta-analysis. Eight [ 13 , 16 – 20 , 26 , 27 ] of them reported that HCP5 was up-regulated in cancer tissues and function as the oncogenes. Therefore, these eight studies were pooled for analysis.…”

“…As shown in Fig. 3 , three studies [ 13 , 16 , 17 ] explored the digestive system carcinoma and five studies [ 18 – 20 , 26 , 27 ] explored the non-digestive system carcinoma. The results of the forest plot suggested that regardless of the digestive system carcinoma or non-digestive system carcinoma, up-regulated HCP5 expression in tumor tissues was correlated with poor OS (digestive system carcinoma, HR = 0.41; 95% CI 0.26–0.65, P = 0.0001; non-digestive system carcinoma, HR = 0.50; 95% CI 0.36–0.71, P < 0.0001, Fig.…”

“…For example, one study found that HCP5 level was decreased in skin cutaneous melanoma, suggesting HCP5 could function as a tumor suppressor and suppresses melanoma development by regulating RARRES3 gene expression via sponging miR-1286 [ 15 ]. Clinically, most evidences have showed that HCP5 overexpression is associated with the clinicopathological characteristics and prognosis of various cancers, including gastric cancer [ 16 , 17 ], non-small cell lung cancer [ 18 ], renal cell carcinoma [ 19 ] and osteosarcoma [ 20 ]. Meanwhile, only one study reported that downregulation of HCP5 was associated with a poor prognosis, advanced tumor stage, positive distal metastasis and lymph node metastasis [ 15 ].…”