Circular RNA circPIP5K1A contributes to cancer stemness of osteosarcoma by miR-515-5p/YAP axis

Pengxu Shi,Qingsheng Guo,Yueting Li

doi:10.1186/s12967-021-03124-6

Abstract

BackgroundOsteosarcoma is a common type of bone tumors and frequently occurs in children and adolescents. Cancer stem cells (CSCs) are a unique sub-type of self-renewal cancer cells and the stemness of cancer cells are involved in the spread, recurrence, metastasis, and even therapeutic resistance. However, the regulation mechanisms of CSCs in osteosarcoma are poorly understood. Circular RNA (circRNA) is a unique sort of non-coding RNAs and widely participate in the modulation of cancer progression.MethodsIn this study, we identified the critical function of circular RNA circPIP5K1A in stemness of osteosarcoma cells.ResultsCircPIP5K1A expression was significantly enhanced in clinical osteosarcoma tissues compared with the adjacent normal tissues. The depletion of circPIP5K1A by siRNA repressed osteosarcoma cell viabilities and induced osteosarcoma cell apoptosis. The suppression of circPIP5K1A attenuated the capabilities of invasion and migration of osteosarcoma cells. The circPIP5K1A knockdown increased E-Cadherin expression and decreased Vimentin expression in osteosarcoma cells. The sphere formation abilities of osteosarcoma cells were repressed by the depletion of circPIP5K1A. The CD133+CD44+ cell population of osteosarcoma cells was reduced by circPIP5K1A knockdown. The expression of ALDH1 and Nanog was decreased by the inhibition of circPIP5K1A in osteosarcoma cells. Mechanically, circPIP5K1A enhanced YAP expression by targeting miR-515-5p. MiR-515-5p inhibited stemness of osteosarcoma cells. The CSCs properties of osteosarcoma cells were repressed by circPIP5K1A knockdown or miR-515-5p mimic, while miR-515-5p inhibitor or YAP overexpression reversed circPIP5K1A knockdown-induced repression. Tumor xenograft analysis in nude mice demonstrated that the depletion of circPIP5K1A represses osteosarcoma cell growth in vivo.ConclusionIn conclusion, we identified that circular RNA circPIP5K1A contributed to cancer stemness of osteosarcoma by miR-515-5p/YAP axis. Targeting circPIP5K1A may be considered as a potential therapeutic strategy for osteosarcoma treatment.

Highlights

Osteosarcoma is a common type of bone tumors and frequently occurs in children and adolescents
The expression of circPIP5K1A is enhanced in clinical osteosarcoma tissues and contributes to osteosarcoma cell proliferation in vitro In order to confirm the association of circPIP5K1A with osteosarcoma, we detected circPIP5K1A expression in clinical osteosarcoma samples
We found that circPIP5K1A expression was significantly enhanced in clinical osteosarcoma tissues (n = 45) relative to the adjacent normal tissues (n = 45) (Fig. 1A)

Summary

Introduction

Osteosarcoma is a common type of bone tumors and frequently occurs in children and adolescents. Cancer stem cells (CSCs) are a unique sub-type of self-renewal cancer cells and the stemness of cancer cells are involved in the spread, recurrence, metastasis, and even therapeutic resistance. Osteosarcoma is a form of bone tumor most frequently occurs in children and adolescents, especially in children [1]. The acquired resistance to standard therapy highlights the urgent need to discover novel therapeutic regimens. Cancer stem cells (CSC) is a unique sub-type of self-renewal cancer cells that participate in the spread, recurrence, metastasis, and even therapeutic resistance [3]. Patients with osteosarcoma who has finished the first therapy would somehow develop a distant metastasis, which implies the possible involvement of CSCs [4]. Targeting the stemness of osteosarcoma maybe a promising area to discover new therapeutical targets

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Discussion

Conclusion