LINC01268 promotes epithelial-mesenchymal transition, invasion and metastasis of gastric cancer via the PI3K/Akt signaling pathway and targeting MARCKS

Ling-Han Tang; Peng-Cheng Ye; Lin Yao; Ya-Jun Luo; Wang Tan; Wan-Ping Xiang; Zi-Lin Liu; Ling Tan; Jiang-Wei Xiao

doi:10.4251/wjgo.v15.i8.1366

LINC01268 promotes epithelial-mesenchymal transition, invasion and metastasis of gastric cancer via the PI3K/Akt signaling pathway and targeting MARCKS

World J Gastrointest Oncol. 2023 Aug 15;15(8):1366-1383. doi: 10.4251/wjgo.v15.i8.1366.

Authors

Ling-Han Tang¹, Peng-Cheng Ye², Lin Yao², Ya-Jun Luo³, Wang Tan⁴, Wan-Ping Xiang⁵, Zi-Lin Liu¹, Ling Tan⁶, Jiang-Wei Xiao⁷

Affiliations

¹ Department of Gastrointestinal Surgery, Clinical Medical College and the First Affiliated Hospital of Chengdu Medical College, Chengdu 610000, Sichuan Province, China.
² Department of Gastrointestinal Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China.
³ Department of Gastrointestinal Surgery, Sichuan Cancer Hospital, Chengdu 610000, Sichuan Province, China.
⁴ Department of Gastrointestinal Surgery, Yaan People's Hospital, Yaan 625000, Sichuan Province, China.
⁵ Department of Thoracic Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China.
⁶ Department of Surgery, People's Hospital Affiliated to Chongqing Three Gorges Medical College, Chongqing 404041, China.
⁷ Department of Gastrointestinal Surgery, Clinical Medical College and the First Affiliated Hospital of Chengdu Medical College, Chengdu 610000, Sichuan Province, China. xiaojiangwei2018@163.com.

Abstract

Background: Long non-coding RNAs (lncRNAs) with differential expression characteristics have been found to be closely related to the tumorigenesis and development of gastric cancer (GC), but their specific mechanisms and roles still need to be further elucidated.

Aim: To investigate the expression of LINC01268 in GC and its mechanism of affecting GC progression.

Methods: Real-time quantitative polymerase chain reaction was used to detect the expression of LINC01268 in GC tissues, cell lines and plasma. The Kaplan-Meier method was used to evaluate the value of LINC01268 in the prognostication of GC patients. An receiver operating characteristic curve was constructed to evaluate the value of LINC01268 in the diagnosis of GC. Transwell migration and invasion assays and wound healing assays were used to confirm the effect of LINC01268 on the invasion and migration of GC cells. The regulatory relationship between LINC01268 and myristoylated alanine rich protein kinase C substrate (MARCKS), the PI3K/Akt signaling pathway, and the epithelial-mesenchymal transition (EMT) process in GC was demonstrated by western blot analysis.

Results: The expression of LINC01268 was increased in GC tissues and cell lines. The expression level of LINC01268 was significantly correlated with lymph node metastasis, TNM stage, and tumor differentiation in patients with GC. Over-expression of LINC01268 indicated a poor prognosis for patients with GC, and it had a certain auxiliary diagnostic value for GC. In vitro functional experiments proved that the abnormal expression of LINC01268 further activated the PI3K/Akt signaling pathway and promoted EMT by targeting and regulating MARCKS and ultimately promoted the invasion and metastasis of GC.

Conclusion: This study elucidates that LINC01268 in GC may be an oncogene that further activates the PI3K/Akt signaling pathway and EMT by targeting and regulating MARCKS, and ultimately promotes the invasion and metastasis of GC. LINC01268 may be a potential effective target for the treatment of GC.

Keywords: Gastric cancer; Invasion; LINC01268; Long non-coding RNA; Metastasis; Myristoylated alanine rich protein kinase C substrate.