OIP5-AS1/CD147/TRPM7 axis promotes gastric cancer metastasis by regulating apoptosis related PI3K-Akt signaling

Jianpeng Chen; Wei Wang; Yujie Zhang; Caixia Wang; Weibo Wang; Aiming Zheng

doi:10.3389/fonc.2023.1221445

OIP5-AS1/CD147/TRPM7 axis promotes gastric cancer metastasis by regulating apoptosis related PI3K-Akt signaling

Front Oncol. 2023 Dec 13:13:1221445. doi: 10.3389/fonc.2023.1221445. eCollection 2023.

Authors

Jianpeng Chen¹, Wei Wang², Yujie Zhang³, Caixia Wang¹, Weibo Wang¹, Aiming Zheng¹

Affiliations

¹ Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
² Department of Oncology, Dongying Hospital of Traditional Chinese Medicine, Dongying, China.
³ Department of Outpatient, Guangzhou University, Guangzhou, China.

Abstract

Background: To explore the mechanism of OIP5-AS1/CD147/TRPM7 axis to gastric cancer (GC) metastasis.

Methods: Bioinformatic analysis was performed to pick up the candidate genes associated with regulation GC metastasis. Using GC cell lines, AGS and MKN-45 as research objects, identify the effect of candidate genes on GC metastasis, judge cell proliferation status by MTT assay and cell clone number, and detect cell migration by Transwell and Wound-healing assay. The molecular mechanism of CD147/OIP5/TRPM7 axis regulating GC metastasis was further explored by RNA sequencing. The key signaling pathways were subsequently verified by flow cytometry and WB.

Results: Bioinformatic analysis suggested OIP5-AS1/CD147/TRPM7 axis may be involving in GC metastasis. The RNA interference experiment proved that after gene interference, the proliferation ability of GC cells decreased significantly (P<0.05), which was manifested in the reduction of the number of cell clones. In addition, the migration ability of GC cells was also affected, which was based on the results of Wound Healing (P<0.05). CD147, OIP5-AS1 and TRPM7 all have harmful effects on GC cells. The relationship between OIP5-AS1 and CD147/TRPM7 was detected by RNA immunoprecipitation. Moreover, the RNA sequencing data indicated that CD147/OIP5-AS1/TRPM7 may coordinately regulate the PI3K-AKT pathway related to GC cell apoptosis, thereby affecting the proliferation and migration of GC cells. After RNA interference, the level of apoptosis increased both in AGS and MKN-45 cells. Meanwhile, the expression of pro-apoptotic proteins Caspase9 and BAX were up-regulated (P<0.05). In addition, the expression of PI3K and AKT proteins was reduced (P<0.05). The mouse tumorigenesis experiment corroborated the results of the in vitro study.

Conclusion: OIP5-AS1/CD147/TRPM7 axis reduces GC cell proliferation by regulating apoptosis associated with PI3K-AKT signaling, further affecting cancer metastasis.

Keywords: CD147; OIP5-AS1; PI3K-Akt; TRPM7; gastric cancer; metastasis.