Long Non-Coding RNA AC118344.1 Promotes Gastric Cancer Cell Proliferation, Invasion, and Metastasis via AKT2 and Its Downstream Molecules HK2 and MMP2

Lixia Cai; Yangji Xue; Jianzu Ding; Bin Zheng

doi:10.2147/CMAR.S281608

Long Non-Coding RNA AC118344.1 Promotes Gastric Cancer Cell Proliferation, Invasion, and Metastasis via AKT2 and Its Downstream Molecules HK2 and MMP2

Cancer Manag Res. 2020 Dec 8:12:12613-12621. doi: 10.2147/CMAR.S281608. eCollection 2020.

Authors

Lixia Cai^#¹, Yangji Xue^#², Jianzu Ding^{2

3}, Bin Zheng^{2

3}

Affiliations

¹ Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
² Huanglong Science and Education Center, Hangzhou Medical College, Hangzhou, People's Republic of China.
³ Zhejiang Academy of Medical Sciences, Hangzhou, People's Republic of China.

^# Contributed equally.

Abstract

Background: Gastric cancer (GC) is a highly occurring cancer with poor prognosis. Reports indicate that long non-coding RNA (LncRNA) potentially regulates tumor progression. Herein, we aim to explore the effect of LncRNA AC118344.1 on the progression of gastric cancer.

Methods: Overexpression and knockout experiments were used to clarify the potential molecular signaling mechanisms induced by AC118344.1. CCK-8, transwell and in vivo metastasis assay were used to detect the function of AC118344.1 in AGS and SGC-7901 cells. Additionally, shRNA silencing techniques, qRT-PCR and Western blot assay were used to explore the relationship between AC118344.1, AKT2, and its downstream molecules.

Results: Upregulating the expression of AC118344.1 induces cell proliferation, invasion in vitro, and lung metastasis in vivo whereas downregulating the expression of AC118344.1 inhibits these effects. Besides, silencing the expression of AC118344.1 downregulated the expression of AKT2 in both the two cells. On the other hand, silencing the expression of AKT2 by shRNA was unable to downregulate the expression of AC118344.1 in both the gastric cancer cells. Also, AC118344.1 regulated AKT2 via its downstream molecules including HK2 and MMP2.

Conclusion: AC118344.1 promotes gastric cancer cell proliferation and invasion and lung metastasis in nude mice by upregulating the expression of AKT2 and its downstream molecules (HK2 and MMP2). Therefore, our findings provide a novel mechanism of the AC118344.1-AKT2-HK2/MMP2 axis in regulating the development of gastric cancer cells.

Keywords: AKT2; gastric cancer; invasion; lncRNA AC118344.1; metastasis; proliferation.