Zhang Peng, Cao Peihua, Zhu Xiaofeng, Pan Mingxin, Zhong Kebo, He Rui, Li Yang, Jiao Xingyuan, Gao Yi
Department of Hepatobiliary Surgery II, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, Guangdong, P. R. China.
Organ Transplant Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, P. R. China.
Oncotarget. 2017 May 16;8(20):33137-33143. doi: 10.18632/oncotarget.16561.
Gallbladder carcinoma (GBC) is the most common malignancy of the bile duct and patients with GBC have extremely poor prognoses. Increasing evidence indicates that long non-coding RNAs (lncRNAs) regulate diverse cellular processes, including cell growth, differentiation, apoptosis, and cancer progression. However, the function of lncRNAs in the progression of GBC remains largely unknown. Here, we reported that HOXA cluster antisense RNA2 (HOXA-AS2) was upregulated in GBC. In vitro experiments revealed that HOXA-AS2 knockdown significantly inhibited GBC cells proliferation by causing G1 arrest and promoting apoptosis, whereas HOXA-AS2 overexpression promoted cell growth. Further functional assays indicated that HOXA-AS2 overexpression significantly promoted GBC cell migration and invasion by promoting EMT. Taken together, our study demonstrates that HOXA-AS2 could act as a functional oncogene in GBC, as well as a potential therapeutic target to inhibit GBC metastasis.
胆囊癌(GBC)是胆管最常见的恶性肿瘤,GBC患者的预后极差。越来越多的证据表明,长链非编码RNA(lncRNAs)调节多种细胞过程,包括细胞生长、分化、凋亡和癌症进展。然而,lncRNAs在GBC进展中的功能仍 largely未知。在此,我们报道HOXA簇反义RNA2(HOXA-AS2)在GBC中上调。体外实验表明,HOXA-AS2敲低通过导致G1期阻滞和促进凋亡显著抑制GBC细胞增殖,而HOXA-AS2过表达促进细胞生长。进一步的功能分析表明,HOXA-AS2过表达通过促进上皮-间质转化(EMT)显著促进GBC细胞迁移和侵袭。综上所述,我们的研究表明HOXA-AS2可能作为GBC中的功能性癌基因,也是抑制GBC转移的潜在治疗靶点。