Abstract
Molecular signaling pathways play a significant role in the regulation of biological mechanisms, and their abnormal expression can provide the conditions for cancer development. The signal transducer and activator of transcription 3 (STAT3) is a key member of the STAT proteins and its oncogene role in cancer has been shown. STAT3 is able to promote the proliferation and invasion of cancer cells and induces chemoresistance. Different downstream targets of STAT3 have been identified in cancer and it has also been shown that microRNA (miR), long non-coding RNA (lncRNA) and other molecular pathways are able to function as upstream mediators of STAT3 in cancer. In the present review, we focus on the role and regulation of STAT3 in gastric cancer (GC). miRs and lncRNAs are considered as potential upstream mediators of STAT3 and they are able to affect STAT3 expression in exerting their oncogene or onco-suppressor role in GC cells. Anti-tumor compounds suppress the STAT3 signaling pathway to restrict the proliferation and malignant behavior of GC cells. Other molecular pathways, such as sirtuin, stathmin and so on, can act as upstream mediators of STAT3 in GC. Notably, the components of the tumor microenvironment that are capable of targeting STAT3 in GC, such as fibroblasts and macrophages, are discussed in this review. Finally, we demonstrate that STAT3 can target oncogene factors to enhance the proliferation and metastasis of GC cells.
Highlights
Gastric cancer (GC) is one of the leading causes of death worldwide and its incidence rate is different among nations [1,2,3]
signal transducer and activator of transcription 3 (STAT3) upregulates the expression of MALAT1, leading to progression and proliferation
MiR-17 reduces the expression of pro-survival factors, such as Bcl-2, and induces apoptosis via STAT3 downregulation
Summary
Gastric cancer (GC) is one of the leading causes of death worldwide and its incidence rate is different among nations [1,2,3]. A large body of evidence has been provided about the factors leading to GC progression It seems that complex molecular pathways are the most important ones in GC malignancy [8]. In GC cells, lncRNA LINC00511 reduces the expression of microRNA (miR)-124-3p to induce PDK4 This axis leads to an increase in the proliferation and progression of GC cells [14]. In addition to the identification of molecular pathways, there have been attempts to target them using anti-tumor compounds It seems that anti-tumor compounds, such as chrysin, psoralen and tivatinib, are able to induce apoptosis in GC cells and suppress their angiogenesis and migration through the downregulation of vascular endothelial growth factor (VEGF) [25,26,27]. We represent how anti-tumor drugs can target STAT3 in suppressing GC progression and metastasis
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