Dataset Information

Circular RNA circHIPK3 Promotes Cell Metastasis through miR-637/STAT3 Axis in Osteosarcoma.

ABSTRACT: Recent studies have suggested that circular RNAs play an important role in the progression of various cancers. However, few studies have revealed the great value of circRNAs in the diagnosis and prognosis prediction of osteosarcoma (OS). In this study, we performed experiments with the human OS cell lines and the results showed that the expression of circHIPK3 in OS cell lines was significantly upregulated compared to that in the normal cell line. In addition, the results showed that circHIPK3 could promote the migration, invasion, and growth of OS cells. Furthermore, miR-637 was identified as a target of circHIPK3, while STAT3 was targeted by miR-637. circHIPK3 could promote STAT3 expression via interacting with miR-637 in OS cells. In conclusion, our research uncovered an important role of the circHIPK3/miR-637/STAT3 pathway in the migration and invasion of OS cells and suggested that circHIPK3 may be a prognostic marker and a promising therapeutic target for OS.

SUBMITTER: Huang Z

PROVIDER: S-EPMC7397379 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Circular RNA circHIPK3 Promotes Cell Metastasis through miR-637/STAT3 Axis in Osteosarcoma.

Huang Zhongyue Z Yuan Chunyan C Gu Huijie H Cheng Xiangyang X Zhou Kaifeng K Xu Jun J Yin Xiaofan X Xia Jiangni J

BioMed research international 20200724

Recent studies have suggested that circular RNAs play an important role in the progression of various cancers. However, few studies have revealed the great value of circRNAs in the diagnosis and prognosis prediction of osteosarcoma (OS). In this study, we performed experiments with the human OS cell lines and the results showed that the expression of circHIPK3 in OS cell lines was significantly upregulated compared to that in the normal cell line. In addition, the results showed that circHIPK3 c ...[more]

PMID: 32775413

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Project description:Accumulating evidence has indicated that circular RNAs (circRNAs) serve crucial roles in the progression of a diverse range of different types of cancer, including osteosarcoma (OS). The present study determined the expression pattern and function of circRNA homeodomain interacting protein kinase 3 (circHIPK3), a novel circular RNA, in OS. It was revealed that circHIPK3 expression was upregulated in OS tissue samples and OS cell lines. A localization assay revealed that circHIPK3 was primarily located in the cytoplasm. Using loss‑of‑function proliferation and Transwell assays, the present study revealed that circHIPK3‑knockdown suppressed OS cell proliferation, migration and invasion. Furthermore, the present study screened potential microRNAs that may interact with circHIPK3. It was revealed that microRNA‑637 (miR‑637) expression was downregulated in OS according to a Gene Expression Omnibus data analysis. In addition, the present study demonstrated that miR‑637 expression was downregulated in OS cell lines. A fluorescence in situ hybridization assay revealed that both miR‑637 and circHIPK3 were located in the cytoplasm. An in‑depth mechanism investigation demonstrated that circHIPK3 expression was inversely correlated with miR‑637 expression, and that circHIPK3 was a target of miR‑637. In addition, it was revealed that histone deacetylase 4 (HDAC4) was another downstream target gene of miR‑637, as demonstrated using a luciferase assay. It was revealed that miR‑637 suppressed OS cell proliferation, migration and invasion via targeting of HDAC4. Finally, the present study demonstrated that circHIPK3 sponged miR‑637 to promote HDAC4 expression and OS cell proliferation, migration and invasion. In conclusion, the present study uncovered the role of the circHIPK3/miR‑637/HDAC4 axis in OS cell proliferation, migration and invasion. It was demonstrated that circHIPK3 promoted OS cell proliferation, migration and invasion by modulating miR‑637/HDAC4 signaling.

Project description:BackgroundCircular RNAs (circRNAs) are involved in diverse processes that drive cancer development. However, the expression landscape and mechanistic function of circRNAs in osteosarcoma (OS) remain to be studied.MethodsBioinformatic analysis and high-throughput RNA sequencing tools were employed to identify differentially expressed circRNAs between OS and adjacent noncancerous tissues. The expression level of circ_001422 in clinical specimens and cell lines was measured using qRT-PCR. The association of circ_001422 expression with the clinicopathologic features of 55 recruited patients with OS was analyzed. Loss- and gain-of-function experiments were conducted to explore the role of circ_001422 in OS cells. RNA immunoprecipitation, fluorescence in situ hybridization, bioinformatics database analysis, RNA pulldown assays, dual-luciferase reporter assays, mRNA sequencing, and rescue experiments were conducted to decipher the competitive endogenous RNA regulatory network controlled by circ_001422.ResultsWe characterized a novel and abundant circRNA, circ_001422, that promoted OS progression. Circ_001422 expression was dramatically increased in OS cell lines and tissues compared with noncancerous samples. Higher circ_001422 expression correlated with more advanced clinical stage, larger tumor size, higher incidence of distant metastases and poorer overall survival in OS patients. Circ_001422 knockdown markedly repressed the proliferation and metastasis and promoted the apoptosis of OS cells in vivo and in vitro, whereas circ_001422 overexpression exerted the opposite effects. Mechanistically, competitive interactions between circ_001422 and miR-195-5p elevated FGF2 expression while also initiating PI3K/Akt signaling. These events enhanced the malignant characteristics of OS cells.ConclusionsCirc_001422 accelerates OS tumorigenesis and metastasis by modulating the miR-195-5p/FGF2/PI3K/Akt axis, implying that circ_001422 can be therapeutically targeted to treat OS.

Dataset Information

Circular RNA circHIPK3 Promotes Cell Metastasis through miR-637/STAT3 Axis in Osteosarcoma.

Publications

Circular RNA circHIPK3 Promotes Cell Metastasis through miR-637/STAT3 Axis in Osteosarcoma.

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