Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China.
Shanghai Institution of Medical Imaging, Shanghai, China.
RNA Biol. 2021 Dec;18(12):2513-2530. doi: 10.1080/15476286.2021.1930755. Epub 2021 Jun 10.
Pancreatic cancer has the worst prognosis of all common cancers. Pancreatic cancer cells have a metabolic advantage due to their swiftly adaptive responses to hypoxic and low-nutrient medium. This advantage contributes to the aggressivity of pancreatic cancer. In this study, lncRNA MIR210HG was abnormally upregulated within pancreatic cancer. It acted as a key oncogenic regulator of pancreatic cancer aggressiveness and glycolysis. Knockdown of MIR210HG significantly inhibited the aggressive phenotype of pancreatic cancer cells and inhibited the growth of xenograft tumours. More importantly, MIR210HG knockdown inhibited pancreatic cancer cell glycolysis via regulating the glycolysis-related hexokinase 2 (HK2) and Pyruvate kinase muscle isozyme M2 (PKM2) expression. Compared with the MIR210HG knockdown group, miR-125b-5p inhibition promoted the aggressive phenotypes and glycolysis of pancreatic cancer cells. Furthermore, the effects of MIR210HG knockdown on HK2 and PKM2 expression, pancreatic cancer cell aggressive phenotypes, and glycolysis were significantly reversed by miR-125b-5p inhibition. In tissue samples, MIR210HG expression was negatively correlated with miR-125b-5p levels and positively correlated with HK2 and PKM2 expression. miR-125b-5p expression was negatively correlated with HK2 and PKM2 expression. In conclusion, MIR210HG affected the phenotypes of pancreatic cancer cells, including proliferation, invasion, migration, and glycolysis, via modulating the miR-125b-5p/HK2/PKM2 axis.
胰腺癌是所有常见癌症中预后最差的一种。由于胰腺癌细胞能够迅速适应缺氧和低营养环境，因此具有代谢优势。这种优势有助于胰腺癌的侵袭性。在这项研究中，lncRNA MIR210HG 在胰腺癌中异常上调。它作为胰腺癌侵袭性和糖酵解的关键致癌调节剂发挥作用。MIR210HG 的敲低显著抑制了胰腺癌细胞的侵袭表型，并抑制了异种移植瘤的生长。更重要的是，MIR210HG 的敲低通过调节糖酵解相关的己糖激酶 2（HK2）和丙酮酸激酶肌肉同工酶 M2（PKM2）表达来抑制胰腺癌细胞的糖酵解。与 MIR210HG 敲低组相比，miR-125b-5p 的抑制促进了胰腺癌细胞的侵袭表型和糖酵解。此外，MIR210HG 敲低对 HK2 和 PKM2 表达、胰腺癌细胞侵袭表型和糖酵解的影响，通过 miR-125b-5p 的抑制显著逆转。在组织样本中，MIR210HG 的表达与 miR-125b-5p 的水平呈负相关，与 HK2 和 PKM2 的表达呈正相关。miR-125b-5p 的表达与 HK2 和 PKM2 的表达呈负相关。总之，MIR210HG 通过调节 miR-125b-5p/HK2/PKM2 轴影响胰腺癌细胞的表型，包括增殖、侵袭、迁移和糖酵解。
