Cervical cancer (CC) is one of the most common cancers among women with high recurrence rates all over the world. Recently, the molecular mechanism of CC has been gradually uncovered in accumulating reports. This study aimed to investigate the function and upstream regulation mechanism of pyruvate dehydrogenase kinase 4 (PDK4) in CC cells, which was verified as an oncogene in several cancers. Through RT‐qPCR assay, we discovered that PDK4 was highly expressed in CC cells. Then, it was demonstrated in function assays that PDK4 facilitated CC cell proliferation and invasion, but inhibited CC cell apoptosis. Next, we sought to determine the upstream genes of PDK4, and miR‐103a‐3p was identified to target PDK4. Then, through bioinformatics tools and a range of mechanism assays, long intergenic non‐protein coding RNA 662 (LINC00662) was verified as the sponge of miR‐103a‐3p. Moreover, LINC00662 positively modulated PDK4 expression via competitively binding to miR‐103a‐3p in CC cells. Subsequently, rescue assays demonstrated that LINC00662 accelerated CC cell proliferation and inhibited cell apoptosis through upregulating PDK4. Furthermore, forkhead box A1 (FOXA1) was verified to activate transcription of both LINC00662 and PDK4. Taken together, our study revealed a novel ceRNA pattern of LINC00662/miR‐103a‐3p/PDK4 with FOXA1 as a transcription factor of LINC00662 and PDK4 in CC cells.

中文翻译：

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LINC00662通过海绵miR-103a-3p和上调PDK4调节宫颈癌细胞增殖、侵袭和凋亡

宫颈癌 (CC) 是全世界女性中最常见的癌症之一，复发率高。近来，CC的分子机制在越来越多的报道中逐渐被揭示。本研究旨在研究丙酮酸脱氢酶激酶 4 (PDK4) 在 CC 细胞中的功能和上游调控机制，该细胞在多种癌症中被证实为致癌基因。通过RT-qPCR分析，我们发现PDK4在CC细胞中高表达。然后，在功能测定中证明PDK4促进CC细胞增殖和侵袭，但抑制CC细胞凋亡。接下来，我们试图确定 PDK4 的上游基因，并且 miR-103a-3p 被鉴定为靶向 PDK4。然后，通过生物信息学工具和一系列机制分析，长基因间非蛋白质编码 RNA 662 (LINC00662) 被证实为 miR-103a-3p 的海绵。此外，LINC00662 通过与 CC 细胞中的 miR-103a-3p 竞争性结合来正向调节 PDK4 的表达。随后，救援试验表明 LINC00662 通过上调 PDK4 加速 CC 细胞增殖并抑制细胞凋亡。此外，叉头盒 A1 (FOXA1) 被证实可以激活 LINC00662 和 PDK4 的转录。总之，我们的研究揭示了 LINC00662/miR-103a-3p/PDK4 的新 ceRNA 模式，其中 FOXA1 作为 CC 细胞中 LINC00662 和 PDK4 的转录因子。救援试验表明，LINC00662 通过上调 PDK4 加速 CC 细胞增殖并抑制细胞凋亡。此外，叉头盒 A1 (FOXA1) 被证实可以激活 LINC00662 和 PDK4 的转录。总之，我们的研究揭示了 LINC00662/miR-103a-3p/PDK4 的新 ceRNA 模式，其中 FOXA1 作为 CC 细胞中 LINC00662 和 PDK4 的转录因子。救援试验表明，LINC00662 通过上调 PDK4 加速 CC 细胞增殖并抑制细胞凋亡。此外，叉头盒 A1 (FOXA1) 被证实可以激活 LINC00662 和 PDK4 的转录。总之，我们的研究揭示了 LINC00662/miR-103a-3p/PDK4 的新 ceRNA 模式，其中 FOXA1 作为 CC 细胞中 LINC00662 和 PDK4 的转录因子。