MicroRNA‑96 expression induced by low‑dose cisplatin or doxorubicin regulates chemosensitivity, cell death and proliferation in gastric cancer SGC7901 cells by targeting FOXO1

Abstract

MicroRNA-96 (miR-96) is transcriptionally associated with the induction of chemoresistance following chemotherapy by targeting to FOXO1 mRNA at one of two predicted binding sites in its 3'-untranslated region sequence. The upregulation of miR-96 is associated with a high risk of chemoresistance. Nevertheless, the mechanism by which miR-96 is upregulated remains largely undefined. In the present study, the gastric cancer SGC7901 cell line was treated with different doses of the chemotherapeutic agents cisplatin and doxorubicin. miR-96 expression was analyzed by reverse transcription-quantitative polymerase chain reaction at different time points. Western blot and chromatin immunoprecipitation were performed to analyze the expression levels of the target gene. The effects of miR-96 on chemosensitivity were assessed by a carboxyfluorescein succinimidyl ester/propidium iodide labeling assay, and its effects on proliferation were assessed by Cell Counting Kit-8 or EdU staining assays. The results demonstrated that treatment with a low dose of either chemotherapeutic agent induced miR-96 expression. Upregulation of miR-96 caused the post-transcriptional repression of FOXO1 expression. Decreases in FOXO1 protein levels led to a decrease in the transcriptional activity of the cyclin-dependent kinase inhibitor 1A (CDKN1A, also known as p21) promoter region, and thus the expression of p21 was downregulated in a tumor protein p53-independent manner. As a result, induction of miR-96 expression caused chemoresistance and promoted proliferation in SGC7901 cells. Taken together, the results of the present study revealed that treatment with cisplatin or doxorubicin could induce expression of miR-96 at certain doses. Upregulation of miR-96 is partially associated with chemoresistance and miR-96 can also promote cell proliferation by repressing p21.

Colorectal cancer cell-derived CCL20 recruits regulatory T cells to promote chemoresistance via FOXO1/CEBPB/NF-κB signaling

“…Targeting the FOXO1/CEBPB/NF-κB/CCL20 axis in tumors may provide a novel potential therapeutic strategy for controlling CRC. MicroRNA-96 expression induced by low-dose cisplatin or doxorubicin regulates chemosensitivity, cell death, and proliferation in gastric cancer SGC7901 cells by targeting FOXO1 [52]. Piva et al showed that functional validation of the anaplastic lymphoma kinase signature identifies CEBPB as a critical target gene [53].…”

Identification of microRNA‐96‐5p as a postoperative, prognostic microRNA predictor in nonviral hepatocellular carcinoma

“…Upregu- Extensive studies have shown that miR-96-5p is upregulated in various types of cancer, including bladder cancer, breast cancer, colorectal cancer, gastric cancer, and non-small-cell lung cancer, as well as HCC. 13,[22][23][24][25][32][33][34][35][36][37][38] It was also shown by in vitro analyses using corresponding cancer cell lines that miR-96-5p promotes proliferation and invasion and inhibits apoptosis, suggesting that it acts as an oncogenic miRNA. In contrast to these studies, downregulation of miR-96-5p has been reported repeatedly in pancreatic cancer.…”

miR‐96‐5p regulates wound healing by targeting BNIP3/FAK pathway

“…miR-96-5p was reported to promote gastric, prostate, and cervical cancers. 16,17 Additionally, miR-96-5p modulates cell proliferation, invasion, and migration in different diseases. 18,19 However, the role of miR-96-5p in wound healing has not been illustrated.…”