XTP1 facilitates the growth and development of gastric cancer by activating CDK6

Kang Li; Rulan Ma; Lei Meng; Qing Wang; Jun Cao; Dawei Yuan; Tuanhe Sun; Li Kang; Nan Hao; Haonan Wang; Kun Zhu

doi:10.21037/atm-22-5933

XTP1 facilitates the growth and development of gastric cancer by activating CDK6

Ann Transl Med. 2023 Jan 31;11(2):97. doi: 10.21037/atm-22-5933.

Authors

Kang Li¹, Rulan Ma¹, Lei Meng¹, Qing Wang², Jun Cao¹, Dawei Yuan¹, Tuanhe Sun¹, Li Kang³, Nan Hao¹, Haonan Wang¹, Kun Zhu¹

Affiliations

¹ Department of Surgical Oncology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
² Department of Surgery, University of Virginia, Charlottesville, VA, USA.
³ Department of Thoracic Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Abstract

Background: Hepatitis B virus X protein (XTP1) is overexpressed in tumor tissues and regulates cancer progression. However, the molecular mechanism of XTP1 in gastric cancer (GC) is poorly understood. Hence, we aimed to dissect the underlying role of XTP1 in the development of GC.

Methods: Lentiviruses were constructed and transfected into GC cells to upregulate or downregulate gene expression. The expressions of proteins in GC cells or tumor tissues were assessed by quantitative reverse transcription polymerase chain reaction (RT-qPCR), Western blotting, immunohistochemistry (IHC) assay, or the Gene Expression Profiling Interactive Analysis (GEPIA) database. Cell proliferation was assessed via methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, Celigo cell counting assay, cell cycle analysis, and colony formation assay. Cell apoptosis was assessed by flow cytometry. The apoptosis-related proteins were evaluated using the human apoptosis antibody array. GC cell migration was detected by scratch wound-healing assays and Transwell migration assays. Potential downstream molecules were identified by the human GeneChip assay combined with bioinformatics analysis.

Results: We found that XTP1 is overexpressed in GC tissues and is positively related to its pathological grade. XTP1 knockdown restrained the growth and migration of GC cells, while XTP1 overexpression promoted cell proliferation and suppressed apoptosis. A mechanistic study indicated that XTP1 knockdown inhibited cyclin-dependent kinase 6 (CDK6) expression and that CDK6 might be a potential downstream molecule of XTP1. Further study confirmed that CDK6 depletion also suppressed GC cell proliferation and migration and increased GC cell apoptosis. Moreover, rescue experiments verified that CDK6 knockdown abated the promotion of XTP1 overexpression on GC progression.

Conclusions: XTP1 facilitated the development and progression of GC cells by activating CDK6. Therefore, the XTP1-CDK6 axis might be a potential therapeutic target for GC.

Keywords: CDK6; XTP1; gastric cancer (GC); therapeutic target; tumor promoter.