CBX2 is a functional target of miRNA let‐7a and acts as a tumor promoter in osteosarcoma

Abstract

Osteosarcoma is the most common type of primary malignant tumor of skeletal with poor prognosis in children and adolescents. Accumulating evidence indicates that CBX2 is overexpressed in multiple human neoplasm and play a critical role in tumorigenesis and progression. However, its functional role and upstream regulation mechanism in osteosarcoma remain unknown. In the present study, tissue microarray (TMA) analysis was performed to determine the association between CBX2 expression and clinical prognosis of osteosarcoma patients by immunohistochemistry. We also investigated the functional role of CBX2 using small interfering RNA (siRNA) in vitro and in vivo. Additionally, we confirmed the direct binding between CBX2 and let‐7a via qPCR, western blot and luciferase reporter assay. We found that CBX2 is dramatically upregulated in osteosarcoma tissues and high CBX2 expression was correlated with metastasis, recurrence, and chemotherapy response, as well as unfavorable prognosis in patients with osteosarcoma. Similar results were observed in a sarcoma cohort from The Cancer Genome Atlas (TCGA) dataset. Further experiments revealed that CBX2 knockdown significantly impeded osteosarcoma cell proliferation and invasion ability in vitro, and suppressed the tumor growth in tumor xenografts model. Mechanistically, we confirmed that CBX2 is a functional target of miRNA let‐7a. Overexpression of let‐7a inhibits osteosarcoma cell proliferation, which was reversed by CBX2 overexpression. Taken together, our study demonstrates that let‐7a/CBX2 plays a crucial role in osteosarcoma progression. CBX2 could serve as a promising prognostic biomarker and potential therapeutic target for osteosarcoma patients.

CBX2 depletion inhibits the proliferation, invasion and migration of gastric cancer cells by inactivating the YAP/β-catenin pathway

“…CBX2, a member of chromobox family, is an essential regulator of cancer progression and the cell cycle ( 28 ). It has been reported that CBX2 exerts an oncogenic effect on osteosarcoma progression and promotes osteosarcoma cell proliferation and metastasis ( 29 ). A previous study demonstrated that CBX2 knockdown markedly suppressed the proliferation of hepatocellular carcinoma cells and promoted apoptosis ( 12 ).…”

CASC9 Facilitates Cell Proliferation in Bladder Cancer by Regulating CBX2 Expression

“…Chromobox homolog 2 (CBX2), one of the member proteins in CBX family, is a necessary regulator of gene expression [40]. Increasing evidence indicates that abnormal expression of CBX2 plays important roles in various cancers, such as prostate cancer, osteosarcoma, and breast cancer [41, 42]. Interestingly, we discovered that CBX2 served as the downstream target gene of miR-497-5p, constituting the CASC9/miR-497-5p/CBX2 axis.…”

CBX2 Induces Glioma Cell Proliferation and Invasion Through the Akt/PI3K Pathway

“…Recently, studies have shown that the expression of CBX2 is closely related to tumorigenesis and tumor development. Some studies have shown that the expression of CBX2 in osteosarcoma tissue is signi cantly increased, and the degree of the increase is closely related to metastasis, postoperative recurrence, chemotherapy reaction and adverse prognosis [16]. In advanced serous ovarian cancer, the expression of CBX2 was signi cantly increased.…”