Inhibition of apoptosis by miR‑122‑5p in α‑fetoprotein‑producing gastric cancer

Abstract

α-Fetoprotein (AFP)-producing gastric cancer (AFPGC) is recognized as one of the most aggressive tumors with subsequent poor prognosis compared with common gastric cancer (GC) subtypes. However, the molecular mechanism remains to be elucidated. We previously identified that miR-122-5p could be a useful biomarker in AFPGC patients. We examined herein the biological function of miR-122-5p and the molecular mechanism underlying tumor progression in AFPGC. We used the AFPGC cell line (FU97) and miR-122-5p inhibitor to examine the function of miR-122-5p. Moreover, we investigated the possible targets of miR-122-5p. The expression level of miR-122-5p was significantly increased in the FU97 cell line than in common GC cell lines. Also, suppression of miR-122-5p significantly reduced AFP levels and proliferation in AFPGC through an induction of apoptosis. Western blotting revealed that the expression of anti-apoptotic protein (Bcl-2) was decreased and that of pro-apoptotic protein (caspase-3) was increased in miR-122-5p suppression of FU97. Moreover, we revealed that FOXO3 was an important target of miR-122-5p in AFPGC, which inhibited apoptosis and subsequently manifested aggressiveness. In conclusion, miR-122-5p inhibited apoptosis and facilitated tumor progression by targeting FOXO3 in AFPGC, which indicates the possibility of miR-122-5p as a potential therapeutic target in AFPGC.

Circular RNA circMAN2B2 promotes growth and migration of gastric cancer cells by down‐regulation of miR‐145

“…14,15 The expression of miRNAs is related to the biological processes of human cancers, such as cell growth, proliferation, differentiation, apoptosis, metastasis, and drug-resistance. [29][30][31][32] MiR-145 is one of such miRNAs and has been reported as a tumor inhibitor in various cancers, such as cervical carcinoma, 33 esophageal squamous cell carcinoma (ESCC), 34 colorectal cancer, 35 prostate cancer, 36 and GC. 37 It was proved to inhibit GC cells growth, migration, and metastasis.…”

Diverse roles of FOXO family members in gastric cancer

“…Identification of the mechanism of apoptosis induction provides potential therapeutic strategies for malignant tumors. In an α-fetoprotein (AFP)-producing GC (AFPGC) model, miR-122-5p inhibited apoptosis and promoted tumor progression by directly targeting FOXO3[ 97 ]. The transcription factor RUNX3 binds to two RUNX binding elements (RBE1 and RBE2) in the promoter region of the Bim gene, which encodes a pro-apoptotic protein.…”

The importance of precision medicine in modern molecular oncology

“…If the concentration of AFP increases, some severe diseases, such as abnormal dendritic cells metabolism, even liver, stomach, pancreas cancer, and AFP-producing gastric cancer, will follow. [17][18][19][20] Carcinoembryonic antigen (CEA), an acidic glycoprotein, is related to cervical carcinoma, cystadenocarcinoma, BC, and colorectal cancer (CRC). [21][22][23] There are other markers, such as human epidermal growth factor receptor 2 (HER2), fibrinogen C domain containing 1 (FIBCD1), and poly ADP-ribose polymerases (PARPs), which are closely connected to BC, gastric cancer, and nonsmall-cell lung cancer.…”

“…For example, α‐fetoprotein (AFP) is a target marker for some tumor‐related albuminoid proteins. If the concentration of AFP increases, some severe diseases, such as abnormal dendritic cells metabolism, even liver, stomach, pancreas cancer, and AFP‐producing gastric cancer, will follow 17‐20 . Carcinoembryonic antigen (CEA), an acidic glycoprotein, is related to cervical carcinoma, cystadenocarcinoma, BC, and colorectal cancer (CRC) 21–23 .…”