title: Esophageal squamous cell carcinoma cell proliferation induced by exposure to low concentration of cigarette smoke extract is mediated via targeting miR-101-3p/COX-2 pathway.
abstract: Cigarette smoke has been implicated as a major risk factor for esophageal squamous cell carcinoma (ESCC). Several lines of evidence have suggested that the promoting effect of cigarette smoking extract (CSE) on ESCC is mediated by upregulation of cyclooxygenase-2 (COX-2) expression. Yet, the underlying molecular and cellular mechanisms of how CSE stimulates COX-2 expression and facilitates ESCC development are largely unknown. In the present study, we revealed microRNA (miR)-101-3p expression was downregulated upon exposure to low concentration of CSE in Eca109 cancer cells, and suppression of miR-101-3p was required for low CSE-induced cell proliferation, presenting as overexpression of miR-101-3p reversing CSE stimulated cancer cell growth. Luciferase assay revealed that COX-2 was a direct target for miR-101-3p and overexpression of miR-101-3p decreased cellular COX-2 protein expression. Furthermore, we found that COX-2 inhibitor and knockdown of COX-2 by siRNA interference could abolish CSE-induced cell proliferation, indicating that promotion of cancer cell proliferation by low concentration of CSE was dependent on COX-2 activity. Finally, downregulation of miR-101-3p expression and upregulation of COX-2 was found in ESCC specimens from patients with smoking history. Taken together, our findings revealed a new post-transcriptional mechanism by which CSE regulated COX-2 expression to favor cancer cell proliferation, suggesting miR-101-3p as a potential biomarker and therapeutic target for smoke-related ESCC.
authors.affiliation: Department of Gastroenterology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Gong
authors.affiliation: Department of Gastroenterology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chu
authors.affiliation: Department of Gastroenterology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Meili
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Jirong
authors.initials: J
authors.lastname: Huo
authors.affiliation: Department of Gastroenterology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Lv
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D000077277:Esophageal Squamous Cell Carcinoma; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects; D012906:Smoke / Q000009:adverse effects*; D062789:Tobacco Products / Q000009:adverse effects
chemical_list: C534072:MIRN101 microRNA, human; D035683:MicroRNAs; D012906:Smoke; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human