Mucin 3A's Promotion of the Proliferation and Migration of Gastric Cancer Cells Through Activation of the mTOR Pathway

Altern Ther Health Med. 2024 May 17:AT9871. Online ahead of print.

Abstract

Context: Gastric cancer (GC) is a common and life-threatening gastrointestinal malignancy. Although mucin 3A (MUC3A) is an essential oncogenic factor in several cancers, limited information is available on its expression in GC tissues and its impact on prognosis.

Objective: The study aimed to characterize MUC3A in GC and to explore its potential involvement in regulating GC cells' behavior through the mammalian target of rapamycin (mTOR) signaling pathway.

Design: The research team conducted a retrospective genetic analysis.

Setting: The study took place as Huzhou Central Hospital, an Affiliated Central Hospital of Huzhou University in Huzhou, Zhejiang, China.

Participants: Participants were 47 patients with GC who had received treatment at the department of general surgery at the hospital and who gave consent for the use of their tissue samples for the genetic analysis.

Outcome measures: The research team: (1) performed a differential analysis of MUC3A using GC and normal tissue samples purchased from the American Type Culture Collection; (2) investigated the exposure of cancer tissues to MUC3A and its effects in the tumor, node, metastasis (TNM) stages of GC, using the real-time quantitative polymerase chain reaction (rt-qPCR) method; (3) performed clone formation and conducted transwell assays by knocking down or overexpressing MUC3A to analyze the effects on the behavior of GC cells; and (4) assessed the content of related marker proteins and the phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) pathway proteins, using a Western blot analysis.

Results: A high level of MUC3A existed in GC tissues, and it was associated with TNM staging. Silencing of the MUC3A inhibited GC-cell migration and proliferation, and MUC3A overexpression had the opposite effect. The addition of agonist M05856 restored the inhibitory effect of silencing MUC3A on GC cell proliferation and migration, suggesting that MUC3A regulates GC cells' behavior through the PI3K/Akt/mTOR pathway.

Conclusions: MUC3A plays an oncogenic role in GC and may regulate GC cell behavior through the PI3K/Akt/mTOR pathway.