circ-LDLRAD3 Knockdown Reduces Cisplatin Chemoresistance and Inhibits the Development of Gastric Cancer with Cisplatin Resistance through miR-588 Enrichment-Mediated SOX5 Inhibition
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background/Aims: Chemoresistance is a common event after cancer chemotherapy, which is associated with the deregulation of circular RNAs (circRNAs). The objective of this study was to clarify the role of circ-LDLRAD3 in cisplatin (DDP)-resistant gastric cancer (GC). Methods: The expression of circ-LDLRAD3, miR-588, and SRY-box transcription factor 5 (SOX5) mRNA was detected by quantitative real-time polymerase chain reaction. Cell viability and the half maximal inhibitory concentration (IC50) value were measured by CCK8 assay. Cell proliferation was assessed by colony formation and EdU assays. Cell apoptosis and cell invasion were assessed by flow cytometry assay and transwell assay, respectively. The expression of SOX5 protein was detected by Western blotting. A xenograft model was established to verify the role of circ-LDLRAD3 in vivo. Exosomes were isolated by differential centrifugation and identified by transmission electron microscopy and the expression of exosome-related proteins. Results: circ-LDLRAD3 was overexpressed in DDP-resistant GC tissues and cells. circ-LDLRAD3 knockdown decreased the IC50 of DDP-resistant cells and suppressed cell proliferation, survival and invasion. miR-588 was a target of circ-LDLRAD3, and miR-588 inhibition attenuated the inhibition of DDP resistance, proliferation, survival and invasion in DDP-resistant GC cells caused by circ-LDLRAD3 knockdown. SOX5 was a target of miR-588, and the inhibition of the DDP resistance, proliferation, survival and invasion of DDP-resistant GC cells by miR-588 restoration was largely rescued SOX5 overexpression. circ-LDLRAD3 knockdown inhibited DDP resistance and tumor growth in vivo. circ-LDLRAD3 was overexpressed in exosomes isolated from DDP-resistant GC cells. Conclusions: circ-LDLRAD3 knockdown reduced DDP resistance and blocked the malignant development of DDP-resistant GC by modulating the miR-588/SOX5 pathway.
Abstract
Background/Aims: Chemoresistance is a common event after cancer chemotherapy, which is associated with the deregulation of circular RNAs (circRNAs). The objective of this study was to clarify the role of circ-LDLRAD3 in cisplatin (DDP)-resistant gastric cancer (GC). Methods: The expression of circ-LDLRAD3, miR-588, and SRY-box transcription factor 5 (SOX5) mRNA was detected by quantitative real-time polymerase chain reaction. Cell viability and the half maximal inhibitory concentration (IC50) value were measured by CCK8 assay. Cell proliferation was assessed by colony formation and EdU assays. Cell apoptosis and cell invasion were assessed by flow cytometry assay and transwell assay, respectively. The expression of SOX5 protein was detected by Western blotting. A xenograft model was established to verify the role of circ-LDLRAD3 in vivo. Exosomes were isolated by differential centrifugation and identified by transmission electron microscopy and the expression of exosome-related proteins. Results: circ-LDLRAD3 was overexpressed in DDP-resistant GC tissues and cells. circ-LDLRAD3 knockdown decreased the IC50 of DDP-resistant cells and suppressed cell proliferation, survival and invasion. miR-588 was a target of circ-LDLRAD3, and miR-588 inhibition attenuated the inhibition of DDP resistance, proliferation, survival and invasion in DDP-resistant GC cells caused by circ-LDLRAD3 knockdown. SOX5 was a target of miR-588, and the inhibition of the DDP resistance, proliferation, survival and invasion of DDP-resistant GC cells by miR-588 restoration was largely rescued SOX5 overexpression. circ-LDLRAD3 knockdown inhibited DDP resistance and tumor growth in vivo. circ-LDLRAD3 was overexpressed in exosomes isolated from DDP-resistant GC cells. Conclusions: circ-LDLRAD3 knockdown reduced DDP resistance and blocked the malignant development of DDP-resistant GC by modulating the miR-588/SOX5 pathway.
참고문헌 (24)
- Bray F, "Global cancer statistics 2018 : GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185countries", CA Cancer J Clin, 68, pp.394~424 (2018)
- Li Z, "Role of long non-coding RNAs in the chemoresistance of gastric cancer : a systematic review", Onco Targets Ther, 14, pp.503~518 (2021)
- Wagner AD, "Chemotherapy for advanced gastric cancer", Cochrane Database Syst Rev, (3), pp.CD004064~ (2010)
- Hong L, "MicroRNAs in gastrointestinal cancer : prognostic significance and potential role in chemoresistance", Expert Opin Biol Ther, 14, pp.1103~1111 (2014)
- Braicu C, "Comprehensive analysis of circular RNAs in pathological states : biogenesis, cellular regulation, and therapeutic relevance", Cell Mol Life Sci, 76, pp.1559~1577 (2019)
- Fang X, "CircRNAs and its relationship with gastric cancer", J Cancer, 10, pp.6105~6113 (2019)
- Cui C, "Functions and mechanisms of circular RNAs in cancer radiotherapy and chemotherapy resistance", Mol Cancer, 19, pp.58~ (2020)
- Huang X, "Circular RNA AKT3 upregulates PIK3R1 to enhance cisplatin resistance in gastric cancer via miR-198 suppression", Mol Cancer, 18, pp.71~ (2019)
- Harrandah AM, "Emerging microRNAs in cancer diagnosis, progression, and immune surveillance", Cancer Lett, 438, pp.126~132 (2018)
- Panda AC, "Circular RNAs act as miRNA sponges", Adv Exp Med Biol, 1087, pp.67~79 (2018)
- Lee S, "Post-transcriptional stimulation of gene expression by microRNAs", Adv Exp Med Biol, 768, pp.97~126 (2013)
- Zhou X, "MicroRNA-588 regulates invasion, migration and epithelial-mesenchymal transition via targeting EIF5A2 pathway in gastric cancer", Cancer Manag Res, 10, pp.5187~5197 (2018)
- You J, "SOX5 promotes cell invasion and metastasis via activation of Twist-mediated epithelialmesenchymal transition in gastric cancer", Onco Targets Ther, 12, pp.2465~2476 (2019)
- Fang QL, "Targeted inhibition of CCL22 by miR-130a-5p can enhance the sensitivity of cisplatin-resistant gastric cancer cells to chemotherapy", Cancer Manag Res, 12, pp.3865~3875 (2020)
- Yang F, "Circular RNA circ-LDLRAD3as a biomarker in diagnosis of pancreatic cancer", World J Gastroenterol, 23, pp.8345~8354 (2017)
- Yao J, "Downregulation of circular RNA circ-LDLRAD3 suppresses pancreatic cancer progression through miR-137-3p", PTN axis, 2019, pp.239, 116871~
- Xue M, "Circular RNA circ-LDLRAD3 serves as an oncogene to promote non-small cell lung cancer progression by upregulating SLC1A5 through sponging miR-137", RNA Biol, 17, pp.1811~1822 (2020)
- Wang Y, "Circ-LDLRAD3 enhances cell growth, migration, and invasion and inhibits apoptosis by regulating miR-224-5p", NRP2 axis in gastric cancer, 2021, pp.66, 3862~3871
- Kok VC, "Cancer-derived exosomes : their role in cancer biology and biomarker development", Int J Nanomedicine, 15, pp.8019~8036 (2020)
- Jalalian SH, "Exosomes, new biomarkers in early cancer detection", Anal Biochem, 571, pp.1~13 (2019)
- Chen Y, "miR-588 is a prognostic marker in gastric cancer", Aging(Albany NY), 13, pp.2101~2117 (2020)
- Yu M, "MicroRNA-588is downregulated and may have prognostic and functional roles in human breast cancer", Med Sci Monit, 23, pp.5690~5696 (2017)
- Liu R, "LncRNA GSEC promotes the proliferation, migration and invasion by sponging miR-588", EIF5A2 axis in osteosarcoma, 2020, pp.532, 300~307
- Ding S, "MicroRNA‑539 inhibits the proliferation and migration of gastric cancer cells by targeting SRY‑box 5gene", Mol Med Rep, 20, pp.2533~2540 (2019)