CircLMTK2 Silencing Attenuates Gemcitabine Resistance in Pancreatic Cancer by Sponging miR-485-5p and to Target PAK1

Yeting Lu; Shuping Zhou; Gong Cheng; Yi Ruan; Yuan Tian; Kaiji Lv; Shuo Han; Xinhua Zhou

doi:10.1155/2022/1911592

CircLMTK2 Silencing Attenuates Gemcitabine Resistance in Pancreatic Cancer by Sponging miR-485-5p and to Target PAK1

J Oncol. 2022 Aug 24:2022:1911592. doi: 10.1155/2022/1911592. eCollection 2022.

Authors

Yeting Lu¹, Shuping Zhou², Gong Cheng¹, Yi Ruan¹, Yuan Tian¹, Kaiji Lv¹, Shuo Han³, Xinhua Zhou¹

Affiliations

¹ Department of General Surgery, Ningbo Medical Center Lihuili Hospital, The Affiliated Lihuili Hospital, Ningbo University, Ningbo 315100, Zhejiang, China.
² Ningbo College of Health Sciences, Ningbo 315100, Zhejiang, China.
³ Department of Healthcare Security and Price Management, Ningbo Medical Center Lihuili Hospital, The Affiliated Lihuili Hospital, Ningbo University, Ningbo 315100, Zhejiang, China.

Abstract

Pancreatic cancer (PC) has a high degree of malignancy and poor prognosis, and countless patients have distant metastasis when diagnosed. Gemcitabine (GEM) chemotherapy is one of the main ways of treatment. However, PC cells have been displayed chemoresistance to GEM during treatment. Circular RNAs (circRNAs) have been demonstrated to be the most popular diagnostic and prognostic biomarkers in PC with GEM resistance. Here, we assessed the potential of circLMTK2 in the GEM resistance of PC cells. Functional assays were implemented to measure the impacts of circLMTK2 on the proliferation, migration/invasion, and apoptosis of GEM-resistant PC cells. Bioinformatics analysis and mechanical experiments displayed the underlying mechanism of circLMTK2 in GEM-resistant PC cells. We found that circLMTK2 was upregulated in PC and GEM-resistant PC tissues and cells. CircLMTK2 knockdown suppressed proliferation, invasion, migration, and enhanced apoptosis in GEM-resistant PC cells. Moreover, circLMTK2 silencing could decrease GEM resistance-associated tumor size in vivo. In terms of mechanism, circLMTK2 served as a sponge for miR-485-5p, and miR-485-5p bound to p21 (RAC1) activated kinase 1 (PAK1), which were clarified via the dual-luciferase assay in PC cell lines. We confirmed that circLMTK2 knockdown attenuated GEM-resistant PC cells by regulating PAK1 via miR-485-5p. Our study demonstrated that circLMTK2 may be a novel diagnostic and prognostic biomarker in GEM-resistant PC cells.