Department of Endocrinology, The Second Hospital of Jilin University, Changchun, Jilin, China.
Endokrynol Pol. 2020;71(2):146-152. doi: 10.5603/EP.a2020.0009. Epub 2020 Mar 10.
MicroRNA-1258 (miR-1258) has been shown to play an anti-cancer role in a variety of cancers, but its relationship with papillary thyroid cancer (PTC) has not been reported. The emphasis of this research was to reveal the biological function of miR-1258 in PTC and its potential mechanisms.
We measured miR-1258 expression in PTC cells and the transfection efficiency of miR-1258 mimic and miR-1258 inhibitor by quantitative real-time PCR (qRT-PCR) assay. Cell Counting Kit-8 assay (CCK8) and Transwell experiments were conducted to examine the influences of altering miR-1258 expression on the viability, migration, and invasion of PTC cells. Bioinformatics prediction and dual-luciferase experiment were performed to verify the target gene of miR-1258. Finally, we carried out a rescue assay to verify whether the regulation of miR-1258 on the biological behaviour of PTC cells needs to be achieved by regulating TMPRSS4.
The outcomes revealed that miR-1258 was lowly expressed in PTC cell lines and miR-1258 showed the lowest expression in KTC-1 and the highest expression in B-CPAP among all tested PTC cell lines. Overexpression of miR-1258 inhibited KTC-1 cell viability and ability to migrate and invade, whereas inhibition of miR-1258 in B-CPAP cells has the opposite effect. Furthermore, we affirmed that miR-1258 can directly target TMPRSS4, and miR-1258 can reduce the biological malignant behaviour of PTC cells via regulation of TMPRSS4.
Taken together, our research raised the possibility that miR-1258 was an anti-oncogene, which exerts its anti-cancer function by targeting TMPRSS4. Hence, it may be possible to treat PTC by targeting the miR-1258/TMPRSS4 axis in the future.
MicroRNA-1258(miR-1258)在多种癌症中发挥着抗癌作用,但它与甲状腺乳头状癌(PTC)的关系尚未报道。本研究的重点是揭示 miR-1258 在 PTC 中的生物学功能及其潜在机制。
我们通过实时定量 PCR(qRT-PCR)检测 PTC 细胞中 miR-1258 的表达及 miR-1258 模拟物和 miR-1258 抑制剂的转染效率。细胞计数试剂盒-8(CCK8)和 Transwell 实验检测改变 miR-1258 表达对 PTC 细胞活力、迁移和侵袭的影响。通过生物信息学预测和双荧光素酶实验验证 miR-1258 的靶基因。最后,我们进行了挽救实验,以验证 miR-1258 是否通过调节 TMPRSS4 来调节 PTC 细胞的生物学行为。
研究结果表明,miR-1258 在 PTC 细胞系中低表达,在所有检测的 PTC 细胞系中,KTC-1 中表达最低,B-CPAP 中表达最高。过表达 miR-1258 抑制 KTC-1 细胞活力和迁移侵袭能力,而在 B-CPAP 细胞中抑制 miR-1258 则产生相反的效果。此外,我们证实 miR-1258 可以直接靶向 TMPRSS4,通过调节 TMPRSS4,miR-1258 可以降低 PTC 细胞的恶性生物学行为。
综上所述,我们的研究提出了 miR-1258 可能是一种抑癌基因的可能性,它通过靶向 TMPRSS4 发挥其抗癌功能。因此,未来可能可以通过靶向 miR-1258/TMPRSS4 轴来治疗 PTC。