Li Yu, Wang Liqin, Xu Xiaoyi, Sun Heng, Wu Leilei
Department of Oncology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin City, Heilongjiang Province, 150040, People's Republic of China.
Nursing Teaching and Research Department, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin City, Heilongjiang Province, 150040, People's Republic of China.
Cancer Manag Res. 2021 Oct 1;13:7543-7557. doi: 10.2147/CMAR.S329846. eCollection 2021.
Cisplatin (DDP) treatment is one of the most predominant chemotherapeutic strategies for patients with gastric cancer (GC). LncRNA noncoding RNA HLA complex group 11 (lncRNA HCG11) has been confirmed to promote GC progression. This study attempted to investigate the underlying molecular mechanism of HCG11 in DDP resistance of GC.
qRT-PCR was performed to evaluate the expression of HCG11, microRNA-144-3p (miR-144-3p), and ubiquitin-conjugating enzyme E2 D1 (UBE2D1) in GC. The correlation between HCG11 and clinicopathological features of GC patients was assessed. DDP-resistant GC cells and their parental cells were cultured in different concentrations of DDP. The role of HCG11 for the viability and the half maximal inhibitory concentration (IC50) of DDP in DDP-resistant GC cells was determined by MTT assay. Then, the invasion of DDP-resistant GC cells was measured by transwell assay. Next, a dual-luciferase reporter assay was used to confirm the interactions among HCG11, miR-144-3p, and UBE2D1 in GC.
The expression of HCG11 and UBE2D1 was elevated in tumor tissues of GC patients, but miR-144-3p was declined. HCG11 expression was elevated in DDP-resistant GC patients and is strongly correlated with DDP sensitivity and World Health Organization grade in GC patients. HCG11 knockdown reduced the viability, IC50 of DDP, and invasion of DDP-resistant GC cells. Additionally, HCG11 targeted miR-144-3p and miR-144-3p further targeted UBE2D1. Feedback experiments indicated that low expression of miR-144-3p or overexpression of UBE2D1 mitigated the inhibitory effect of HCG11 depletion on DDP resistance of GC cells.
HCG11 knockdown attenuated DDP resistance of GC cells through via miR-144-3p/UBE2D1 axis, affording a novel therapeutic strategy for GC.
顺铂（DDP）治疗是胃癌（GC）患者最主要的化疗策略之一。长链非编码RNA HLA复合体基因座11（lncRNA HCG11）已被证实可促进胃癌进展。本研究旨在探讨HCG11在胃癌顺铂耐药中的潜在分子机制。
采用qRT-PCR检测胃癌组织中HCG11、微小RNA-144-3p（miR-144-3p）和泛素结合酶E2 D1（UBE2D1）的表达。评估HCG11与胃癌患者临床病理特征的相关性。将顺铂耐药胃癌细胞及其亲本细胞培养于不同浓度的顺铂中。通过MTT法测定HCG11对顺铂耐药胃癌细胞活力和半数最大抑制浓度（IC50）的作用。然后用Transwell法检测顺铂耐药胃癌细胞的侵袭能力。接下来，采用双荧光素酶报告基因实验证实胃癌中HCG11、miR-144-3p和UBE2D1之间的相互作用。
HCG11和UBE2D1在胃癌患者肿瘤组织中的表达升高，但miR-144-3p表达下降。顺铂耐药胃癌患者中HCG11表达升高，且与胃癌患者的顺铂敏感性和世界卫生组织分级密切相关。敲低HCG11可降低顺铂耐药胃癌细胞的活力、顺铂IC50及侵袭能力。此外，HCG11靶向miR-144-3p，而miR-144-3p进一步靶向UBE2D1。反馈实验表明，miR-144-3p低表达或UBE2D1过表达可减轻HCG11缺失对胃癌细胞顺铂耐药的抑制作用。
敲低HCG11通过miR-144-3p/UBE2D1轴减弱胃癌细胞的顺铂耐药性，为胃癌提供了一种新的治疗策略。
