Micro–ribonucleic acids (miRNAs) are a class of conserved small non-coding RNAs (sncRNAs) that post-transcriptionally regulate their downstream target genes. Existing evidence indicates that abnormal expression of mRNAs results in the occurrence and development of pancreatic cancer (PC). In this study, we explored the potential role of miRNA-139 (miR-139) as a biomarker in the monitoring and treatment of PC. We demonstrated that expression of miR-139 was significantly downregulated in PC cells and tissues. In addition, both in vitro and in vivo experiments showed that miR-139 significantly inhibited the growth, migration, and invasion of PC cells. We carried out microarray analysis and transcriptome sequencing to find the potential target of miR-139 in PC cells, and the results showed that miR-139 targeted Ras-like proto-oncogene B (RalB). Luciferase reporter experiments verified that high level of RalB could reverse the proliferation and invasion of PC cells overexpressing miR-139. Using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, we found that miR-139 likely affected PC cell cycle by targeting RalB via the Ral/protein kinase B (Akt) serine/threonine kinase 1 (RAC)/phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) pathway, thus affecting cell proliferation. This presumption was further confirmed in our in vitro and in vivo experiments. Our examination of PC tissues suggested that the expression of miR-139 was negatively correlated with that of RalB. Taken together, our results implied that miR-139 could suppress tumor growth and metastasis in PC by targeting RalB, revealing the potential role of miR-139 as a biomarker for the monitoring and treatment of PC.

微核糖核酸 (miRNA) 是一类保守的小非编码 RNA (sncRNA)，可对下游靶基因进行转录后调控。现有证据表明，mRNAs的异常表达导致胰腺癌（PC）的发生和发展。在本研究中，我们探讨了 miRNA-139 (miR-139) 作为生物标志物在 PC 监测和治疗中的潜在作用。我们证明 miR-139 的表达在 PC 细胞和组织中显着下调。此外，在体外和体内实验表明miR-139显着抑制PC细胞的生长、迁移和侵袭。我们进行了微阵列分析和转录组测序，以寻找 miR-139 在 PC 细胞中的潜在靶点，结果显示 miR-139 靶向Ras样原癌基因 B（RalB）。荧光素酶报告基因实验证实，高水平的RalB可以逆转过表达 miR-139 的 PC 细胞的增殖和侵袭。使用基因本体论 (GO) 和京都基因和基因组百科全书 (KEGG) 分析，我们发现 miR-139 可能通过Ral /蛋白激酶 B ( Akt ) 丝氨酸/苏氨酸激酶 1 ( RAC )靶向RalB来影响 PC 细胞周期)/phosphatidylinositol-4,5-bisphosphate 3-kinase ( PI3K ) 通路，从而影响细胞增殖。这一假设在我们的体外和体内实验中得到了进一步证实。我们对 PC 组织的检查表明 miR-139 的表达与RalB的表达呈负相关。总之，我们的结果表明 miR-139 可以通过靶向RalB抑制 PC 中的肿瘤生长和转移，揭示了 miR-139 作为 PC 监测和治疗的生物标志物的潜在作用。