Dataset Information

Circular RNA circKIF4A facilitates the malignant progression and suppresses ferroptosis by sponging miR-1231 and upregulating GPX4 in papillary thyroid cancer.

ABSTRACT: Circular RNAs (circRNAs) are one type of non-coding RNA. They act as important role in regulating various biological processes in the malignant progression. But we don't clearly know the specific mechanism of the majority circRNAs in papillary thyroid tumor progression. In the current study, we explored circKIF4A and the result showed that it had high expression in papillary thyroid cancer. The functions of circKIF4A were explored by CCK-8, transwell, and mouse xenograft experiments. Knockdown of circKIF4A could suppress papillary thyroid cell growth and migration. In addition, RIP assays and dual luciferase vector reporter assays were further conducted. Our consequence showed circKIF4A facilitated the malignant progress of papillary thyroid tumor by sponging miR-1231 and upregulating GPX4 expression. In conclusion, our study proved that circKIF4A-miR-1231-GPX4 axis played a vital role in cancer proliferation and ferroptosis by competing endogenous RNAs. Therefore, targeting circKIF4A is very likely to be a potential method for treatment of papillary thyroid cancer in the future.

SUBMITTER: Chen W

PROVIDER: S-EPMC8266339 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Circular RNA circKIF4A facilitates the malignant progression and suppresses ferroptosis by sponging miR-1231 and upregulating GPX4 in papillary thyroid cancer.

Chen Wenkuan W Fu Jianchang J Chen Yingle Y Li Yudong Y Ning Li L Huang Dou D Yan Shumei S Zhang Quan Q

Aging 20210621 12

Circular RNAs (circRNAs) are one type of non-coding RNA. They act as important role in regulating various biological processes in the malignant progression. But we don't clearly know the specific mechanism of the majority circRNAs in papillary thyroid tumor progression. In the current study, we explored circKIF4A and the result showed that it had high expression in papillary thyroid cancer. The functions of circKIF4A were explored by CCK-8, transwell, and mouse xenograft experiments. Knockdown o ...[more]

PMID: 34153004

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Project description:As a newly identified circular RNA (circRNA), the role of circBLNK in cancer progression has not been probed. The objective of the present study was to functionally dissect the role of circBLNK in osteosarcoma (OS) tumorigenesis and progression. With regards of the experimental procedure, the levels of mRNAs and proteins were assessed using reverse transcription‑quantitative PCR and western blot analysis, respectively. The subcellular location of circBLNK in OS cells was determined by cell cytosolic/nuclear fractionation assay. Cell ferroptosis ability was assessed through MTT assay. Cell proliferative abilities were assessed by clonogenic and Cell Counting Kit‑8 assays, and cell apoptosis was measured using flow cytometry. The relationships among circBLNK, miR‑188‑3p, and glutathione peroxidase 4 (GPX4) were validated by luciferase reporter and RNA pull‑down assays, as well as RNA immunoprecipitation. The stability of circBLNK and linear BLNK was confirmed using RNase R treatment assay. The association between circBLNK expression and overall survival rate was assessed by Kaplan‑Meier plot. The correlation between the expression levels of circBLNK, miR‑188‑3p, and GPX4 in OS tissues was assessed by Pearson's χ2 test. The results revealed that CircBLNK and GPX4 were significantly upregulated in OS tissues, which predicted the poor prognosis. CircBLNK knockdown led to suppressed cell proliferation and enhanced cell apoptosis, an effect that could be reversed by the inhibition of miR‑188‑3p. In an in vivo circBLNK deficiency model, tumor growth was observed to be markedly suppressed. Moreover, circBLNK deficiency elevated levels of intracellular free iron (Fe2+), malondialdehyde, lipid reactive oxygen species and mitochondrial superoxide, while diminishing mitochondrial membrane potential in Erastin‑treated OS cells, which were eliminated by overexpressing GPX4. Furthermore, mechanistic investigations revealed that circBLNK sponged miR‑188‑3p to regulate the expression of GPX4, thereby affecting OS progression. In conclusion, the present study delineated a new regulatory axis involving circBLNK/miR‑188‑3p/GPX4 in OS progression, adding to the growing evidence that circRNAs are critical gene regulators in cancer progression.

Dataset Information

Circular RNA circKIF4A facilitates the malignant progression and suppresses ferroptosis by sponging miR-1231 and upregulating GPX4 in papillary thyroid cancer.

Publications

Circular RNA circKIF4A facilitates the malignant progression and suppresses ferroptosis by sponging miR-1231 and upregulating GPX4 in papillary thyroid cancer.

Similar Datasets

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