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circPVT1 在口腔鳞状细胞癌中过表达,通过作为 miRNA 海绵促进增殖。

Overexpressed circPVT1 in oral squamous cell carcinoma promotes proliferation by serving as a miRNA sponge.

机构信息

Department of Stomatology, China‑Japan Friendship Hospital, Beijing 100029, P.R. China.

出版信息

Mol Med Rep. 2019 Oct;20(4):3509-3518. doi: 10.3892/mmr.2019.10615. Epub 2019 Aug 26.

Abstract

Circular RNAs (circRNAs) comprise a novel class of widespread non‑coding RNAs that may regulate gene expression in eukaryotes. However, the characterization and function of circRNAs remain elusive in human cancer, including oral squamous cell carcinoma (OSCC). In this study, the expression level of circPVT1 in OSCC was detected and define its functional role in initiation and progression of OSCC. It was identified that circPVT1 was upregulated in OSCC cells and specimens. Knockdown of circPVT1 suppressed cell proliferation as evidenced by Cell Counting kit‑8 assay and elevated Ki‑67 expression. Mechanistically, it was demonstrated that circPVT1 possessed two targeting sites of microRNA (miRNA/miR)‑125b and could effectively sponge miR‑125b to release its downstream mRNA targets. Subsequently, the downstream target signal transducer and activator of transcription 3 (STAT3) was verified as a direct target of miR‑125b and STAT3 expression was regulated by the circPVT1/miR‑125b axis. CircPVT1 functioned as competing endogenous RNA (ceRNA) to increase the STAT3 level and cell proliferation through sponging miR‑125b. In conclusion, circPVT1 regulates cell proliferation and may serve as a promising therapeutic target for OSCC patients. Therefore, silencing of circPVT1 could be a future direction to develop a novel treatment strategy.

摘要

环状 RNA(circRNAs)是一类新型的广泛存在的非编码 RNA,可能在真核生物中调节基因表达。然而,环状 RNA 在人类癌症中的特征和功能仍不明确,包括口腔鳞状细胞癌(OSCC)。在本研究中,检测了 OSCC 中 circPVT1 的表达水平,并定义了其在 OSCC 发生和发展中的功能作用。结果表明,circPVT1 在 OSCC 细胞和标本中上调。circPVT1 敲低抑制了细胞增殖,这一点可通过细胞计数试剂盒-8 检测和升高的 Ki-67 表达得到证明。在机制上,证明 circPVT1 具有两个 microRNA(miRNA/miR)-125b 的靶向位点,并可以有效地吸收 miR-125b 来释放其下游 mRNA 靶标。随后,下游靶信号转导和转录激活因子 3(STAT3)被验证为 miR-125b 的直接靶标,并且 STAT3 的表达受 circPVT1/miR-125b 轴的调节。circPVT1 作为竞争性内源 RNA(ceRNA)通过吸收 miR-125b 来增加 STAT3 水平和细胞增殖。总之,circPVT1 调节细胞增殖,可能成为 OSCC 患者有前途的治疗靶点。因此,沉默 circPVT1 可能是开发新治疗策略的未来方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19d5/6755181/2ecb0e053ddd/MMR-20-04-3509-g00.jpg

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