Chemotherapy is, next to surgery and radiotherapy, the mainstay regimen for the clinical management of gastric cancer. This therapy is, however, heavily compromised by the acquisition of resistance. Here, we aimed to clarify the potential involvement of long non-coding RNA SNGH3 in the acquisition of cisplatin resistance and stemness in gastric cancer.
Cell viability and proliferation were measured using Cell Counting Kit-8 and colony formation assays, respectively. Stem cell-like cell growth was evaluated using a mammosphere formation assay. RNA levels of SNHG2, OCT-4, SOX-2, CD44, miR-3619-5p and ARL2 were determined using qRT-PCR, whereas protein levels of OCT-4, SOX-2, CD44, ARL2, STAT3 and pSTAT3 were determined using Western blotting. Dual luciferase reporter assays were employed to interrogate regulatory interactions between STAT3, SNHG3, miR-3619-5p and ARL2, respectively. Direct binding of STAT3 to the SNHG3 promoter was investigated using a chromatin immunoprecipitation assay.
We found that IL-6 triggered stem cell-like properties in cisplatin-treated gastric cancer cells and activated STAT3, which in turn transcriptionally regulated SNHG3 expression. SNHG3 expression up-regulation positively correlated with cisplatin resistance and stemness of gastric cancer cells, while SNHG3 down-regulation inhibited stem cell-like properties. In addition, we found that SNHG3 up-regulated ARL2 expression through sponging miR-3619-5p, which predominantly mediated the oncogenic properties of SNHG3 in this disease.
Our data indicate an involvement of aberrant SNHG3 over-expression in the acquisition of both cisplatin resistance and stemness of gastric cancer cells, and of the IL-6/STAT3/SNHG3/miR-3619-5p/ARL2 signaling cascade in the oncogenic properties of SNHG3.
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Long non-coding RNA
American Type CultureCollection
Cell Counting Kit-8
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This work was supported by Shanghai Anticancer Association “aoxiang” Project (SACA-AX201901).
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Sun, B., Han, Y., Cai, H. et al. RETRACTED ARTICLE: Long non-coding RNA SNHG3, induced by IL-6/STAT3 transactivation, promotes stem cell-like properties of gastric cancer cells by regulating the miR-3619-5p/ARL2 axis. Cell Oncol. 44, 179–192 (2021). https://doi.org/10.1007/s13402-020-00560-2
- gastric cancer
- stem cell
- cisplatin resistance