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.

中文翻译：

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长的非编码RNA OIP5-AS1通过AKT / ERK信号通路使miR-342-3p海绵化，从而促进胰腺癌细胞的生长。

Opa相互作用蛋白5反义RNA 1（OIP5-AS1）是一种长的非编码RNA（lncRNA），据报道与某些癌症的进展有关。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。这项研究的目的是调查lncRNA OIP5-AS1在胰腺癌中的作用。实时定量PCR分析表明，OIP5-AS1在胰腺癌组织中相对于相邻的非肿瘤组织中高表达。体外功能测定显示，OIP5-AS1的下调或miR-342-3p的过表达抑制胰腺癌细胞的增殖，降低Ki67表达并诱导细胞周期停滞。通过敲低OIP5-AS1，可降低cyclinD1，CDK4和CDK6的表达。此外，我们发现OIP5-AS1充当miR-342-3p海绵来抑制其表达和功能。双荧光素酶测定法确认了OIP5-AS1与miR-342-3p的相互作用，并验证了前梯度2（AGR2）作为miR-342-3p的直接靶标。结果表明，miR-342-3p的耗竭消除了OIP5-AS1敲低对胰腺癌细胞生长的抑制作用。通过沉默miR-342-3p沉默OIP5-AS1敲低胰腺癌细胞，可以逆转Ki67，AGR2，cyclinD1，CDK4，CDK6，p-AKT和p-ERK1 / 2的表达。此外，在胰腺癌的异种移植小鼠模型中，敲除OIP5-AS1可抑制肿瘤的生长。OIP5-AS1通过激活AKT和ERK信号通路诱导胰腺癌进展。因此，