Qu Feng, Zhu Bin, Hu Yi-Lin, Mao Qin-Sheng, Feng Ying
Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Nantong, China.
Department of General Surgery, Rudong Third People's Hospital, Rudong, China.
Cancer Cell Int. 2021 Feb 18;21(1):118. doi: 10.1186/s12935-021-01827-w.
Gastric cancer (GC) is among the most common and deadliest cancers globally. Many long non-coding RNAs (lncRNAs) are key regulators of GC pathogenesis. This study aimed to define the role of HOXA-AS3 in this oncogenic context.
Levels of HOXA-AS3 expression in GC were quantified via qPCR. The effects of HOXA-AS3 knockdown on GC cells function were evaluated in vitro using colony formation assays, wound healing assays and transwell assays. Subcutaneous xenograft and tail vein injection tumor model systems were generated in nude mice to assess the effects of this lncRNA in vivo. The localization of HOXA-AS3 within cells was confirmed by subcellular fractionation, and predicted microRNA (miRNA) targets of this lncRNA and its ability to modulate downstream NF-κB signaling in GC cells were evaluated via luciferase-reporter assays, immunofluorescent staining, and western blotting.
GC cells and tissues exhibited significant HOXA-AS3 upregulation (P < 0.05), and the levels of this lncRNA were found to be correlated with tumor size, lymph node status, invasion depth, and Helicobacter pylori infection status. Knocking down HOXA-AS3 disrupted GC cell proliferation, migration, and invasion in vitro and tumor metastasis in vivo. At a mechanistic level, we found that HOXA-AS3 was able to sequester miR-29a-3p, thereby regulating the expression of LTβR and modulating NF-κB signaling in GC.
HOXA-AS3/miR-29a-3p/LTβR/NF-κB regulatory axis contributes to the progression of GC, thereby offering novel target for the prognosis and treatment of GC.
胃癌（GC）是全球最常见且最致命的癌症之一。许多长链非编码RNA（lncRNA）是胃癌发病机制的关键调节因子。本研究旨在明确HOXA-AS3在这种致癌环境中的作用。
通过qPCR定量检测胃癌中HOXA-AS3的表达水平。使用集落形成试验、伤口愈合试验和Transwell试验在体外评估HOXA-AS3敲低对胃癌细胞功能的影响。在裸鼠中建立皮下异种移植和尾静脉注射肿瘤模型系统，以评估该lncRNA在体内的作用。通过亚细胞分级分离确定HOXA-AS3在细胞内的定位，并通过荧光素酶报告基因试验、免疫荧光染色和蛋白质印迹法评估该lncRNA预测的微小RNA（miRNA）靶标及其调节胃癌细胞下游NF-κB信号传导的能力。
胃癌细胞和组织中HOXA-AS3显著上调（P < 0.05），且发现该lncRNA的水平与肿瘤大小、淋巴结状态、浸润深度和幽门螺杆菌感染状态相关。敲低HOXA-AS3可破坏体外胃癌细胞的增殖、迁移和侵袭以及体内肿瘤转移。在机制层面，我们发现HOXA-AS3能够结合miR-29a-3p，从而调节LTβR的表达并调节胃癌中的NF-κB信号传导。
HOXA-AS3/miR-29a-3p/LTβR/NF-κB调节轴促进胃癌进展，从而为胃癌的预后和治疗提供了新的靶点。
