Lingwa Wang1, Ru Wang1, Tianqiao Huang2, Yifan Yang1, Ling Feng3, Jugao Fang4. 1. Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China. 2. Department of Otolaryngology Head and Neck Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China. 3. Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China. floscar@126.com. 4. Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China. fangjugao@163.com.
Abstract
PURPOSE: To investigate the potential mechanisms of miR-211-3p on induction chemotherapy (IC) sensitivity in hypopharyngeal squamous cell carcinoma (HSCC). METHODS: qRT-PCR was assessed to compare the miR-211-3p expression between IC sensitive and insensitive tumor tissues. The MTT assay was performed to analyze cell proliferation and viability to paclitaxel after alteration of miR-211-3p. Flow cytometry assay was conducted to explore cell apoptosis. Transwell assay was used to explore the effect of miR-211-3p on cell migration. Transcriptome sequencing was then performed to select differentially expressed genes (DEGs) after over-expression of miR-211-3p. GO and KEGG enrichment analyses were conducted to annotate DEGs. PPI analysis was conducted to screen candidate genes. The differential expression and survival status of candidate genes were further validated in TCGA-HNSCC data. The single sample GSEA method was used to investigate the association between downstream genes and immune cell infiltration. RESULTS: miR-211-3p was up-regulated in IC insensitive larynx-hypopharyngeal tumor tissues. Over-expression of miR-211-3p promoted cell proliferation and migration, and inhibited apoptosis. The IC50 value of miR-211-3p overexpression (OE) group was significantly higher than negative control (NC) group treated with paclitaxel, suggesting miR-211-3p enhanced IC insensitivity in HSCC. We found 778 DEG after over-expression of miR-211-3p and 11 significant genes were then identified. Finally, colony stimulating factor 2 (CSF2) and C-C motif chemokine ligand 20 (CCL20) were validated to be significantly high expressed and associated with poorer overall survival in head and neck squamous cell carcinoma, which were involved in TNF signaling pathway and then regulated immune cell infiltration. CONCLUSION: The miR-211-3p could promote HSCC progression and upregulate CSF2/CCL20/TNF signaling to promote IC insensitivity in HSCC, which may provide new ideas for HSCC therapy.
PURPOSE: To investigate the potential mechanisms of miR-211-3p on induction chemotherapy (IC) sensitivity in hypopharyngeal squamous cell carcinoma (HSCC). METHODS: qRT-PCR was assessed to compare the miR-211-3p expression between IC sensitive and insensitive tumor tissues. The MTT assay was performed to analyze cell proliferation and viability to paclitaxel after alteration of miR-211-3p. Flow cytometry assay was conducted to explore cell apoptosis. Transwell assay was used to explore the effect of miR-211-3p on cell migration. Transcriptome sequencing was then performed to select differentially expressed genes (DEGs) after over-expression of miR-211-3p. GO and KEGG enrichment analyses were conducted to annotate DEGs. PPI analysis was conducted to screen candidate genes. The differential expression and survival status of candidate genes were further validated in TCGA-HNSCC data. The single sample GSEA method was used to investigate the association between downstream genes and immune cell infiltration. RESULTS: miR-211-3p was up-regulated in IC insensitive larynx-hypopharyngeal tumor tissues. Over-expression of miR-211-3p promoted cell proliferation and migration, and inhibited apoptosis. The IC50 value of miR-211-3p overexpression (OE) group was significantly higher than negative control (NC) group treated with paclitaxel, suggesting miR-211-3p enhanced IC insensitivity in HSCC. We found 778 DEG after over-expression of miR-211-3p and 11 significant genes were then identified. Finally, colony stimulating factor 2 (CSF2) and C-C motif chemokine ligand 20 (CCL20) were validated to be significantly high expressed and associated with poorer overall survival in head and neck squamous cell carcinoma, which were involved in TNF signaling pathway and then regulated immune cell infiltration. CONCLUSION: The miR-211-3p could promote HSCC progression and upregulate CSF2/CCL20/TNF signaling to promote IC insensitivity in HSCC, which may provide new ideas for HSCC therapy.
Authors: Katrien Van Roosbroeck; Francesca Fanini; Tetsuro Setoyama; Cristina Ivan; Cristian Rodriguez-Aguayo; Enrique Fuentes-Mattei; Lianchun Xiao; Ivan Vannini; Roxana S Redis; Lucilla D'Abundo; Xinna Zhang; Milena S Nicoloso; Simona Rossi; Vianey Gonzalez-Villasana; Rajesha Rupaimoole; Manuela Ferracin; Fortunato Morabito; Antonino Neri; Peter P Ruvolo; Vivian R Ruvolo; Chad V Pecot; Dino Amadori; Lynne Abruzzo; Steliana Calin; Xuemei Wang; M James You; Alessandra Ferrajoli; Robert Orlowski; William Plunkett; Tara M Lichtenberg; Ramana V Davuluri; Ioana Berindan-Neagoe; Massimo Negrini; Ignacio I Wistuba; Hagop M Kantarjian; Anil K Sood; Gabriel Lopez-Berestein; Michael J Keating; Muller Fabbri; George A Calin Journal: Clin Cancer Res Date: 2016-11-30 Impact factor: 12.531
Authors: J Robert Newman; Timothy M Connolly; Elisa A Illing; Meredith L Kilgore; Julie L Locher; William R Carroll Journal: Laryngoscope Date: 2014-09-15 Impact factor: 3.325
Authors: Freddie Bray; Jacques Ferlay; Isabelle Soerjomataram; Rebecca L Siegel; Lindsey A Torre; Ahmedin Jemal Journal: CA Cancer J Clin Date: 2018-09-12 Impact factor: 508.702
Authors: J Xue; Y Chi; Y Chen; S Huang; X Ye; J Niu; W Wang; L M Pfeffer; Z-M Shao; Z-H Wu; J Wu Journal: Oncogene Date: 2015-04-13 Impact factor: 9.867