Dataset Information

A novel circular RNA hsa_circ_0008035 contributes to gastric cancer tumorigenesis through targeting the miR-375/YBX1 axis.

ABSTRACT: Circular RNAs (circRNAs) play an important regulatory role in a variety of human cancers, including gastric cancer. The mechanisms for the circRNAs in gastric cancers are not fully understood. This study aims to uncover the mechanism by which circRNAs regulate gastric cancer tumorigenesis. Among the microarray data, we screened dysregulated circRNAs and identified an up-regulated circRNA, hsa_circ_0008035. Functionally, the hsa_circ_0008035 silencing by the siRNA transfection inhibited the proliferation and invasion of gastric cancer cells. Mechanically, hsa_circ_0008035 acted as a sponge for the miR-375 and absorbed its expression, and miR-375 was found to target YBX1 3'-UTR, constructing a hsa_circ_0008035/miR-375/YBX1 axis. Taken together, these findings are evidence that circRNA hsa_circ_0008035 promotes gastric cancer cell proliferation and invasion by regulating miR-375/YBX1.

SUBMITTER: Huang S

PROVIDER: S-EPMC6511772 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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A novel circular RNA hsa_circ_0008035 contributes to gastric cancer tumorigenesis through targeting the miR-375/YBX1 axis.

Huang Shifang S Zhang Xiaolin X Guan Bingsheng B Sun Peng P Hong Chong Tsz CT Peng Juzheng J Tang Shaohui S Yang Jingge J

American journal of translational research 20190415 4

Circular RNAs (circRNAs) play an important regulatory role in a variety of human cancers, including gastric cancer. The mechanisms for the circRNAs in gastric cancers are not fully understood. This study aims to uncover the mechanism by which circRNAs regulate gastric cancer tumorigenesis. Among the microarray data, we screened dysregulated circRNAs and identified an up-regulated circRNA, hsa_circ_0008035. Functionally, the hsa_circ_0008035 silencing by the siRNA transfection inhibited the proli ...[more]

PMID: 31105852

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Project description:Background:Osteosarcoma (OS) is the most common primary malignancy of bone with a high incidence in children. Circular RNAs (circRNAs) play crucial roles in the carcinogenesis and chemoresistance of OS. In the current work, we focused on the function and mechanism of hsa_circ_0003496 (circ_0003496) in OS progression and chemoresistance. Materials and Methods:The expression levels of circ_0003496, miR-370 and Krüppel-like factor 12 (KLF12) mRNA were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The Cell Counting Kit-8 (CCK-8) assay was used to assess the 50% inhibitory concentration (IC50) value and cell proliferation. Cell migration, invasion and apoptosis were detected by transwell assay and flow cytometry, respectively. Western blot analysis was performed to assess the protein level. Targeted relationships among circ_0003496, miR-370 and KLF12 were validated by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays. Animal studies were carried out to observe the role of circ_0003496 in vivo. Results:Our results indicated that circ_0003496 up-regulation was associated with doxorubicin (DXR) resistance of OS. Circ_0003496 knockdown repressed DXR-resistant OS cell proliferation, migration and invasion, and enhanced apoptosis and DXR sensitivity. Circ_0003496 functioned as a sponge of miR-370, and miR-370 mediated the regulatory effect of circ_0003496 depletion on DXR-resistant OS cell progression and DXR sensitivity. KLF12 was a direct target of miR-370, and miR-370 overexpression suppressed cell progression and enhanced DXR sensitivity by KLF12. Moreover, circ_0003496 protected against KLF12 repression through sponging miR-370. Additionally, circ_0003496 knockdown hampered tumor growth and promoted DXR sensitivity in vivo. Conclusion:Our present work suggested that the knockdown of circ_0003496 suppressed OS progression and enhanced DXR sensitivity at least partially through modulating KLF12 expression via functioning as a miR-370 sponge, highlighting new opportunities for OS management.

Project description:BACKGROUND:Circular RNAs (circRNAs) have emerged as a novel category of non-coding RNA, which exhibit a pivotal effect on regulating gene expression and biological functions, yet how circRNAs function in osteosarcoma (OSA) still demands further investigation. This study aimed at probing into the function of hsa_circ_0000282 in OSA. METHODS:The expressions of circ_0000282 and miR-192 in OSA tissues and cell lines were examined by quantitative real-time polymerase chain reaction (qRT-PCR), and the correlation between the expression level of circ_0000282 and clinicopathological features of OSA patients was analyzed. The expressions of X-linked inhibitor of apoptosis protein (XIAP), B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in OSA cells were assayed by Western blot. The proliferation and apoptosis of OSA cells were examined by CCK-8, BrdU and flow cytometry, respectively. Bioinformatics analysis, dual-luciferase reporter gene assay and RIP experiments were employed to predict and validate the targeting relationships between circ_0000282 and miR-192, and between miR-192 and XIAP, respectively. RESULTS:Circ_0000282 was highly expressed in OSA tissues and cell lines, which represented positive correlation with Enneking stage of OSA patients and negative correlation with tumor differentiation degree. In vitro experiments confirmed that overexpression of circ_0000282 markedly facilitated OSA cell proliferation and repressed cancer cell apoptosis in comparison to control group. Besides, knockdown of circ_0000282 repressed OSA cell proliferation and promoted apoptosis. Additionally, the binding relationships between circ_0000282 and miR-192, and between miR-192 and XIAP were validated. Circ_0000282 indirectly up-regulated XIAP expression by adsorbing miR-192, thereby playing a role in promoting cancer in OSA. CONCLUSION:Circ_0000282 was a novel oncogenic circRNA in OSA. Circ_0000282/miR-192/XIAP axis regulated OSA cell proliferation apoptosis with competitive endogenous RNA mechanism.

Dataset Information

A novel circular RNA hsa_circ_0008035 contributes to gastric cancer tumorigenesis through targeting the miR-375/YBX1 axis.

Publications

A novel circular RNA hsa_circ_0008035 contributes to gastric cancer tumorigenesis through targeting the miR-375/YBX1 axis.

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