scholarly journals STAT3 Pathway in Gastric Cancer: Signaling, Therapeutic Targeting and Future Prospects

Biology ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 126
Author(s):  
Milad Ashrafizadeh ◽  
Ali Zarrabi ◽  
Sima Orouei ◽  
Vahideh Zarrin ◽  
Ebrahim Rahmani Moghadam ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Molecular Pathways ◽  
Molecular Signaling ◽  
Stat Proteins ◽  
Stat3 Signaling ◽  
Non Coding Rna ◽  
Stat3 Signaling Pathway ◽  
Proliferation And Metastasis ◽  
Transcription 3 ◽  
Long Non Coding Rna

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.

scholarly journals Long non‑coding RNA MIAT promotes gastric cancer proliferation and metastasis via modulating the miR‑331‑3p/RAB5B pathway

2020 ◽  
Vol 20 (6) ◽  
pp. 1-1
Author(s):  
Xiao-Mei Li ◽  
Yan-Yan Jiao ◽  
Bao-Hong Luan ◽  
Hong-Xia Wu ◽  
Rong-Rong Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Proliferation ◽  
Non Coding Rna ◽  
Proliferation And Metastasis ◽  
Long Non Coding Rna

Long Non-Coding RNA GATA6-AS1 Inhibits Proliferation and Promotes Apoptosis of Lung Adenocarcinoma Through Sponging miR-331-3p and Regulating SOCS1/JAK2/STAT3 Pathway

2020 ◽  
Author(s):  
Xiaodong Huo ◽  
Huixing Wang ◽  
Ning Jiang ◽  
Kuo Yang ◽  
Bin Huo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Cell Apoptosis ◽  
Luciferase Reporter ◽  
Stat3 Signaling ◽  
Novel Approach ◽  
Non Coding Rna ◽  
Stat3 Signaling Pathway ◽  
Reporter Assays ◽  
Long Non Coding Rna

Abstract Background: Accumulating evidence has indicated the remarkable roles of long non-coding RNAs (lncRNAs) as oncogenes or tumor suppressors in many malignancies. The involvement of lncRNA GATA6-AS1 in cancers remains largely undiscovered. Herein, our research was aimed at elucidating the function and mechanism of GATA6-AS1 in lung adenocarcinoma (LUAD).Methods: Gene expression was measured through qRT-PCR and WB. Cell proliferation ratio was determined using CCK-8 and EdU assays. Cell apoptosis ratio was determined using TUNEL and flow cytometry assays. Molecular interactions were examined through RIP, RNA pull-down and luciferase reporter assays.Results: GATA6-AS1 expression was markedly down-regulated in LUAD cell lines. GATA6-AS1 could inhibit LUAD cell proliferation and promote cell apoptosis. Mechanistically, GATA6-AS1 was identified as the molecular sponge for miR-331-3p, whose knockdown in LUAD cells could reinforce the tumor-suppressing effects of GATA6-AS1 overexpression. Moreover, GATA6-AS1 functions as a competing endogenous RNA (ceRNA) through sequestering miR-331-3p to deregulate SOCS1, thus inhibiting JAK2/STAT3 signaling pathway and suppressing LUAD cell viability.Conclusions: These results demonstrate the tumor-suppressing function and mechanism of lncRNA GATA6-AS1 in LUAD cells. The axis of GATA6-AS1/miR-331-3p/SOCS1/JAK2/STAT3 can be adopted as a novel approach for LUAD treatment.

scholarly journals Long non-coding RNA HOST2 enhances proliferation and metastasis in gastric cancer

Neoplasma ◽  
2019 ◽  
Vol 66 (01) ◽  
pp. 101-108 ◽  
Author(s):  
D. Liu ◽  
M. Y. Zhang ◽  
Z. Chu ◽  
M. Zhang
Keyword(s):  
Gastric Cancer ◽  
Non Coding Rna ◽  
Proliferation And Metastasis ◽  
Long Non Coding Rna

scholarly journals MicroRNA-653-5p Promotes Gastric Cancer Proliferation and Metastasis by Targeting the SOCS6-STAT3 Pathway

2021 ◽  
Vol 8 ◽  
Author(s):  
Zengliang Li ◽  
Hao Fan ◽  
Wangwang Chen ◽  
Jian Xiao ◽  
Xiang Ma ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Janus Kinase ◽  
Migration And Invasion ◽  
Cytokine Signaling ◽  
Cancer Proliferation ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Proliferation And Metastasis

MicroRNAs (miRNAs) are emerging as significant regulators of the tumorigenesis of gastric cancer (GC), and may be effective biomarkers for diagnosis, prognosis, and therapeutic targeting for GC. In this study, miR-653-5p was found to be significantly upregulated in GC tissues, serum, and cell lines and was strongly associated with poor prognosis in patients with GC. Furthermore, miR-653-5p promoted GC cell proliferation and metastasis in vivo and in vitro. Suppressor of cytokine signaling 6 (SOCS6) was directly targeted by miR-653-5p, and SOCS6 attenuated miR-653-5p-mediated GC cell growth, migration, and invasion. In addition, SOCS6-mediated inactivation of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway was also reversed by the administration of miR-653-5p. The findings from this study support a novel regulatory axis between miR-653-5p, SOCS6, and JAK2/STAT3 that may be a target for diagnosis and therapeutic intervention for GC.

scholarly journals Knockdown of long non-coding RNA HOXD-AS1 inhibits gastric cancer cell growth via inactivating the JAK2/STAT3 pathway

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770533 ◽  
Author(s):  
Li Zheng ◽  
Jiangtao Chen ◽  
Zhongyong Zhou ◽  
Zhikuan He
Keyword(s):  
Gastric Cancer ◽  
Cancer Cell ◽  
Colony Formation ◽  
Gastric Cancer Cell ◽  
Janus Kinase ◽  
Signal Transducer ◽  
Janus Kinase 2 ◽  
Non Coding Rna ◽  
Transcription 3 ◽  
Long Non Coding Rna

Long non-coding RNA HOXD-AS1 (HOXD cluster antisense RNA 1) has been demonstrated to be closely associated with the progression of several tumors. However, the biological function of HOXD-AS1 and the underlying molecular mechanism in gastric cancer are still unclear. The expression of HOXD-AS1 in gastric cancer cell lines was evaluated by quantitative real-time polymerase chain reaction. The association of HOXD-AS1 expression and clinical parameters was statistically analyzed by chi-square test. Cell viability, colony formation capacity, and phosphorylation of Janus kinase 2 and signal transducer and activator of transcription 3 in treated SGC-7901 and BGC-823 cells were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony formation assay, and western blot analysis, respectively. The results indicated that HOXD-AS1 was significantly upregulated in gastric cancer cells and clinically involved in tumor size, invasion depth, tumor–node–metastasis stages, regional lymph nodes, lymphatic metastasis, as well as distant metastasis. HOXD-AS1 knockdown dramatically inhibited gastric cancer cell proliferation, colony formation capacity, and phosphorylation of Janus kinase 2 and signal transducer and activator of transcription 3 in vitro. In addition, HOXD-AS1 overexpression significantly promoted gastric cancer cell proliferation and colony formation capacity, whereas both Janus kinase small interfering RNAs and Janus kinase 2 inhibitor AG490 overturned these effects. Furthermore, xenograft assays confirmed the biological function of HOXD-AS1 in vivo. Taken together, our data elucidate that knockdown of HOXD-AS1 dramatically suppresses gastric cancer cell growth by inactivating the Janus kinase 2/signal transducer and activator of transcription 3 pathway in vitro and in vivo, contributing to a better understanding of gastric cancer pathogenesis and providing a possible theoretical foundation for long non-coding RNA–directed diagnosis and therapy against this disease.

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