Department of Pathology, Xiangya Hospital, School of Basic Medical Sciences, Central South University, Changsha, China.
Department of Clinical Laboratory, Liuzhou People's Hospital, Guangxi, China.
Cancer Sci. 2022 Aug;113(8):2560-2574. doi: 10.1111/cas.15399. Epub 2022 Jun 5.
Histone deacetylases (HDACs) are involved in many processes including tumor cell growth and proliferation and regulation of gene expression. To clarify the role of class IIa HDACs in the metastasis of colon adenocarcinoma, we used the class IIa HDAC inhibitor TMP269 and found that it effectively inhibited the migration ability of colon adenocarcinoma cells. Next, we silenced the member of class IIa HDACs and confirmed that the migratory ability of colon adenocarcinoma cells was significantly inhibited by silencing HDAC5 or HDAC7. HDAC5 plays a variety of roles in human cancers. Here, we examined the role of HDAC5 in colon adenocarcinoma. The results indicated that HDAC5 was highly expressed in tumor tissues and negatively correlated with the expression of miR-148a-3p. Moreover, the expression of HDAC5 was correlated with tumor progression. HDAC5 markedly increased the invasion and migration of cancer cells in vitro, an effect that could be inhibited by overexpression of miR-148a-3p. Following an intraperitoneal injection of colon adenocarcinoma cells in athymic nude mice, HDAC5 promoted tumor implant. Together, these findings showed that HDAC5 overexpression in colon adenocarcinoma is consistent with tumor progression and tumor cell migration and the impact of HDAC5 overexpression is reduced by miR-148a-3p.
组蛋白去乙酰化酶(HDACs)参与多种过程,包括肿瘤细胞的生长和增殖以及基因表达的调控。为了阐明 IIa 类 HDAC 在结肠腺癌转移中的作用,我们使用 IIa 类 HDAC 抑制剂 TMP269,发现其能有效抑制结肠腺癌细胞的迁移能力。接下来,我们沉默了 IIa 类 HDACs 的成员,并证实沉默 HDAC5 或 HDAC7 可显著抑制结肠腺癌细胞的迁移能力。HDAC5 在人类癌症中发挥着多种作用。在这里,我们研究了 HDAC5 在结肠腺癌中的作用。结果表明,HDAC5 在肿瘤组织中高表达,与 miR-148a-3p 的表达呈负相关。此外,HDAC5 的表达与肿瘤进展相关。HDAC5 显著增加了体外癌细胞的侵袭和迁移,而 miR-148a-3p 的过表达可抑制这种作用。在裸鼠中进行结肠腺癌细胞的腹腔注射后,HDAC5 促进了肿瘤种植。综上所述,这些发现表明 HDAC5 在结肠腺癌中的过度表达与肿瘤进展和肿瘤细胞迁移一致,而 miR-148a-3p 的过表达可降低 HDAC5 过度表达的影响。