LncRNA STXBP5-AS1 suppresses stem cell-like properties of pancreatic cancer by epigenetically inhibiting neighboring and
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RESEARCH
LncRNA STXBP5‑AS1 suppresses stem cell‑like properties of pancreatic cancer by epigenetically inhibiting neighboring androglobin gene expression Shi Chen1*†, Long Huang1†, Ge Li2†, Funan Qiu1, Yaodong Wang1, Can Yang1, Jingjing Pan1, Zhangwei Wu1, Jiangzhi Chen2* and Yifeng Tian1*
Abstract Previous studies suggest the tumor suppressor role of long non-coding RNA (lncRNA) STXBP5-AS1 in cervical and gastric cancer, but its expression pattern and functional mechanism are still elusive in pancreatic cancer (PC). Relative expression of STXBP5-AS1 in PC both in vivo and in vitro was analyzed by real-time PCR. IC50 of Gemcitabine was determined by the MTT assay. Cell proliferation in response to drug treatment was investigated by colony formation assay. Cell apoptosis was measured by both caspase-3 activity and Annexin V/PI staining. Cell invasion capacity was scored by the transwell assay in vitro, and lung metastasis was examined with the tail vein injection assay. Cell stemness was determined in vitro by sphere formation and marker profiling, respectively, and in vivo by limited dilution of xenograft tumor incidence. Subcellular localization of STXBP5-AS1 was analyzed with fractionation PCR. Association between STXBP5-AS1 and EZH2 was investigated by RNA-immunoprecipitation. The binding of EZH2 on ADGB promoter was analyzed by chromatin immunoprecipitation. The methylation was quantified by bisulfite sequencing. We showed downregulation of STXBP5-AS1 in PC associated with poor prognosis. Ectopic STXBP5-AS1 inhibited chemoresistance and metastasis of PC cells. In addition, STXBP5-AS1 compromised stemness of PC cells. Mechanistically, STXBP5-AS1 potently recruited EZH2 and epigenetically regulated neighboring ADGB transcription, which predominantly mediated the inhibitory effects of STXBP5-AS1 on stem cell-like properties of PC cells. Our study highlights the importance of the STXBP5-EZH2-ADGB axis in chemoresistance and stem cell-like properties of PC. Keywords: Long non-coding RNA, STXBP5-AS1, ADGB, Pancreatic cancer
*Correspondence: [email protected]; [email protected]; [email protected] † Shi Chen, Long Huang, and Ge Li have contributed equally to this work 1 Department of Hepato‑Biliary‑Pancreatic Surgery, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fujian Medical University, No. 134 East Street, Fuzhou 350001, Fujian, China 2 Department of Hepatobiliary Surgery, Union Hospital, Fujian Medical University, Fuzhou 350001, Fujian, China
Background Pancreatic cancer (PC) is one of the most lethal human malignancies with poor prognosis [1]. There are 227,000 deaths claimed by this disease every year globally. Currently, surgical removal and chemotherapy are still the mainstay of clinical management options [2]. However, due to the lack of evident symptom and reliable early diagnosis, PC is frequently diagnosed at late and untreatable stage, which greatly contributes to the relatively unfavorable prognosis [3, 4]. On the other hand, assembled stu
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