Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China.
Department of Gastrointestinal Endoscopy, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, People's Republic of China.
J Physiol Biochem. 2020 May;76(2):301-315. doi: 10.1007/s13105-020-00734-4. Epub 2020 Mar 10.
Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1), a long non-coding RNA (lncRNA), has been reported to link with the progression of some cancers. However, its biological functions and underlying molecular mechanisms in pancreatic cancer are largely unknown. The aim of this study was to investigate the role of lncRNA OIP5-AS1 in pancreatic cancer. Quantitative real-time PCR analysis revealed that OIP5-AS1 is highly expressed in pancreatic cancer tissues versus adjacent non-tumor tissues. In vitro functional assays showed that downregulation of OIP5-AS1 or overexpression of miR-342-3p inhibited the proliferation, decreased Ki67 expression, and induced cell cycle arrest in pancreatic cancer cells. The expression of cyclinD1, CDK4, and CDK6 was decreased by knockdown of OIP5-AS1. Moreover, we found that OIP5-AS1 acted as a miR-342-3p sponge to suppress its expression and function. Dual-luciferase assay confirmed the interaction of OIP5-AS1 and miR-342-3p and verified anterior gradient 2 (AGR2) as a direct target of miR-342-3p. Results showed that depletion of miR-342-3p abolished the inhibitory effects of OIP5-AS1 knockdown on pancreatic cancer cell growth. The expression of Ki67, AGR2, cyclinD1, CDK4, CDK6, p-AKT, and p-ERK1/2 was reversed by silencing of miR-342-3p in pancreatic cancer cells with OIP5-AS1 knockdown. Further, knockdown of OIP5-AS1 suppressed tumor growth in a xenograft mouse model of pancreatic cancer. OIP5-AS1 induced pancreatic cancer progression via activation of AKT and ERK signaling pathways. Therefore, we demonstrate that OIP5-AS1 functions as oncogene in pancreatic cancer and its downregulation inhibits pancreatic cancer growth by sponging miR-342-3p via targeting AGR2 through inhibiting AKT/ERK signaling pathway.
Opa 相互作用蛋白 5 反义 RNA1（OIP5-AS1）是一种长链非编码 RNA（lncRNA），已被报道与一些癌症的进展有关。然而，其在胰腺癌中的生物学功能和潜在分子机制在很大程度上尚不清楚。本研究旨在探讨 lncRNA OIP5-AS1 在胰腺癌中的作用。定量实时 PCR 分析显示，OIP5-AS1 在胰腺癌组织中高表达，而在相邻非肿瘤组织中低表达。体外功能测定表明，下调 OIP5-AS1 或过表达 miR-342-3p 可抑制胰腺癌细胞的增殖，降低 Ki67 表达，并诱导细胞周期停滞。下调 OIP5-AS1 可降低 cyclinD1、CDK4 和 CDK6 的表达。此外，我们发现 OIP5-AS1 作为 miR-342-3p 的海绵体抑制其表达和功能。双荧光素酶报告基因实验证实了 OIP5-AS1 与 miR-342-3p 的相互作用，并验证了前梯度 2（AGR2）是 miR-342-3p 的直接靶标。结果表明，miR-342-3p 的耗竭消除了 OIP5-AS1 下调对胰腺癌细胞生长的抑制作用。在 OIP5-AS1 下调的胰腺癌细胞中，沉默 miR-342-3p 逆转了 Ki67、AGR2、cyclinD1、CDK4、CDK6、p-AKT 和 p-ERK1/2 的表达。此外，OIP5-AS1 的下调抑制了胰腺癌异种移植小鼠模型中的肿瘤生长。OIP5-AS1 通过激活 AKT 和 ERK 信号通路促进胰腺癌的进展。因此，我们证明 OIP5-AS1 在胰腺癌中作为癌基因发挥作用，其下调通过靶向 AGR2 抑制 AKT/ERK 信号通路来抑制 miR-342-3p 的海绵作用从而抑制胰腺癌的生长。
