Correlation between macrophage migration inhibitory factor and autophagy in Helicobacter pylori-associated gastric carcinogenesis

Abstract

The role of macrophage migration inhibitory factor (MIF) and autophagy in gastric cancer is not clear. We determined H. pylori infection status of the subjects and investigated the expression of MIF and autophagy markers (Atg5, LC3A and LC3B) in human gastric tissue at baseline. Then H. pylori eradication was done for H. pylori positive patients and MIF and Atg5 levels were investigated on each follow-up for both H. pylori-eradicated and H. pylori negative patients. Baseline tissue mRNA expression of MIF, Atg5, LC3A and LC3B was measured by real-time PCR in 453 patients (control 165, gastric dysplasia 82, and gastric cancer 206). Three hundred three patients (66.9%) had H. pylori infection at the time of enrollment. Only within H. pylori-positive group, MIF level was significantly elevated in patients with cancer than in control or dysplasia groups (P<0.05). LC3A and LC3B levels also showed significant differences within H. pylori-positive subgroups. H. pylori-positive dysplasia subgroup showed significantly lower (LC3A) (P<0.05) and higher (LC3B) mRNA levels (P<0.05) than in other subgroups. On follow-up, within H. pylori-eradicated group, Atg5 expression increased sequentially from control to dysplasia and cancer subgroups. Multiple linear regression showed autophagy markers (LC3A, LC3B, and Atg5) directly predicted MIF level (adjusted R2 = 0.492, P<0.001). Serial follow-up showed longitudinal increase in Atg5 level in general, with constantly higher levels in H. pylori-eradicated group than in -negative group. Intestinal metaplasia (IM) group initially showed higher Atg5 expression than the IM-negative group. However, it was reversed between the groups eventually because of the lower rate of increase in IM group. These results suggest a role of MIF and autophagy markers and their interaction in H. pylori-associated gastric carcinogenesis.

Marsdenia tenacissima Extract Induces Autophagy and Apoptosis of Hepatocellular Cells via MIF/mToR Signaling

“…MIF was first discovered in the culture medium of active T lymphocytes and macrophages, and it mediates the innate and adaptive immune system to exert immune-regulatory functions [23]. Although recent studies have indicated that MIF is involved in the regulation of autophagy in tumor cells, its role is unclear [24,25].…”

Pulmonary Micro-Ecological Changes and Potential Microbial Markers in Lung Cancer Patients

“…The positive rate of the H . pylori (HP) in gastric cancer patients was positively correlated with the expression of macrophage migration inhibition factor (MIF) ( 59 ). The expression of Mif can promote cell transformation, tumor cell proliferation, and metastasis.…”