Trim14 promotes autophagy and chemotherapy resistance of gastric cancer cells by regulating AMPK/mTOR pathway

Abstract

ObjectiveTo study the relationship between TRIM14 expression and chemotherapy resistance of gastric cancer (GC) cells.MethodsThe expression of TRIM14 in 5‐fluorouracil (5‐FU)‐ and oxaliplation (L‐OHP)‐resistant GC tissues and cells were determined by qRT‐PCR and western blotting. PcDNA3.1‐TRIM14 and shRNA‐TRIM14 vector were transfected to 5‐FU‐resistant GC cells (SGC7901/5‐FU), and the proliferation and apoptosis of cells were measured. Animal experiments on 5‐FU‐resistant GC mice were performed to study the effect of TRIM14 expression on tumor size and weight, GC cell migration, and proliferation. pcDNA3.1‐MK‐3903 plasmid was transfected to SGC7901/5‐FU cells with TRIM14 silence. The cell proliferation and apoptosis were determined. The protein expressions of Trim14, LC3, and BECLIN1 were measured by western blotting.ResultsTRIM14 was significantly upregulated in 5‐FU‐ and L‐OHP‐resistant GC tissues and cells. The overexpression of TRIM14 promoted the proliferation and autophagy of SGC7901/5‐FU cells, and inhibited the apoptosis. Moreover, in vivo experiment verified that the silence of TRIM14 reduced the tumor size and weight, and inhibited the migration and proliferation of GC cells in 5‐FU‐resistant GC mice. The overexpression of MK‐3903 reversed the inhibiting role of TRIM14 knockout on the proliferation and autophagy of SGC7901/5‐FU cells.ConclusionTRIM14 promoted chemotherapy resistance of GC cells by regulating AMPK/mTOR pathway, and may be a new biomarker for treating GC.

Radiofrequency ablation in combination with an mTOR inhibitor restrains pancreatic cancer growth induced by intrinsic HSP70

“…Generally, RFA treatment can elevate the expression of HSP70 in residual cancer cells located in the transition area, then phosphorylate AKT to activate mTOR signaling, which promotes 4EBP1 and p70S6K phosphorylation, and finally accelerates PDAC growth ( Figure 7D ). Considering other regulators of mTOR signaling, such as YAP and AMPK, 41 an mTOR inhibitor was applied to block this pathway. INK-128, a new mTOR inhibitor, can inhibit both phosphorylation of 4EBP1 and p70S6K while the first generation inhibitors can only inhibit p70S6K.…”

The Role of Autophagy in Gastric Cancer Chemoresistance: Friend or Foe?

“…The regulatory proteins of the AMPK pathway have been shown to induce autophagy and chemoresistance ( Table 1). Xiao et al (2020) have suggested that tripartite motif containing 14 (TRIM14) is significantly up-regulated in 5-FU-and OXAresistant gastric cancer tissues and cell lines. Further studies have shown that TRIM14 can promote autophagy and induce chemoresistance by activating the AMPK/mTOR pathway in vivo and in vitro while silencing TRIM14 provides the opposite effects (Xiao et al, 2020).…”

“…Xiao et al (2020) have suggested that tripartite motif containing 14 (TRIM14) is significantly up-regulated in 5-FU-and OXAresistant gastric cancer tissues and cell lines. Further studies have shown that TRIM14 can promote autophagy and induce chemoresistance by activating the AMPK/mTOR pathway in vivo and in vitro while silencing TRIM14 provides the opposite effects (Xiao et al, 2020). Pei et al (2018) have found that metadherin (MTDH) expression in gastric cancer tissues is significantly increased and positively correlated with 5-FU resistance.…”

Title: Expression and content of the LC3B protein in gastric cancers, relationship to mTOR, AMPK expression, clinical and morphological parameters, and the tumor response to neoadjuvant chemotherapy

“…The role of mTOR kinase is also diverse. It integrates various signaling pathways, including AKT/mTOR, activated under the in uence of growth factors and mitogens [Xiao F, 2020]. It is believed that mTOR activation inhibits the development of the self-eating process and is accompanied by protein synthesis processes [Tapia, O.…”