Background: MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) play vital regulatory roles in pancreatic cancer (PC) initiation and progression. We aimed to explore the biological functions and underlying mechanisms of miR-505-3p (miR-505) in PC.

Methods: We first screened miRNA expression profiles using microarray in PC tissues and normal tissues, and then studied the function and underlying mechanism of miR-505. Moreover, we evaluated the regulatory effect of lncRNA LINC01448 on miR-505.

Results: We demonstrated miR-505 that was significantly downregulated in PC tissues. We further revealed that miR-505 significantly inhibited cell proliferation, invasion, sphere formation, glucose consumption, and lactate production by targeting HK2. In addition, overexpression of miR-505 led to tumor growth inhibition in vivo, demonstrating that it acts as a tumor suppressor in PC. LINC01448 was identified as an oncogenic lncRNA that could reduce miR-505 expression. Subsequent studies confirmed that LINC01448 enhanced cell proliferation, invasion, sphere formation, glucose consumption, and lactate production by regulating the miR-505/HK2 pathway.

Conclusions: These findings demonstrated that miR-505, suppressed by LINC01448, could function as a key tumor suppressor by targeting HK2 in PC, elucidating an important role of the LINC01448/miR-505/HK2 pathway in regulating PC glycolysis and progression.

背景：MicroRNA（miRNA）和长非编码RNA（lncRNA）在胰腺癌（PC）的发生和发展中起着至关重要的调节作用。我们旨在探讨miR-505-3p（miR-505）在PC中的生物学功能和潜在机制。

方法：我们首先使用微阵列筛选了PC组织和正常组织中的miRNA表达谱，然后研究了miR-505的功能和潜在机制。此外，我们评估了lncRNA LINC01448对miR-505的调控作用。

结果：我们证明了miR-505在PC组织中显着下调。我们进一步揭示，miR-505通过靶向HK2显着抑制细胞增殖，侵袭，球形成，葡萄糖消耗和乳酸产生。此外，miR-505的过表达导致肿瘤生长受到抑制体内，表明它在PC中起着抑癌作用。LINC01448被鉴定为可降低miR-505表达的致癌lncRNA。随后的研究证实，LINC01448通过调节miR-505 / HK2途径来增强细胞增殖，侵袭，球形成，葡萄糖消耗和乳酸产生。

结论： 这些发现表明，被LINC01448抑制的miR-505可以通过靶向PC中的HK2来充当关键的肿瘤抑制因子，从而阐明了LINC01448 / miR-505 / HK2通路在调节PC糖酵解和进程中的重要作用。