PMID- 31938022 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220412 IS - 1475-2867 (Print) IS - 1475-2867 (Electronic) IS - 1475-2867 (Linking) VI - 20 DP - 2020 TI - Silencing of miR-17-5p suppresses cell proliferation and promotes cell apoptosis by directly targeting PIK3R1 in laryngeal squamous cell carcinoma. PG - 14 LID - 10.1186/s12935-020-1096-3 [doi] LID - 14 AB - BACKGROUND: Increasing evidence has suggested that microRNAs (miRNAs) act as key post-transcriptional regulators in tumor progression. Previous studies have confirmed that miR-17-5p functions as an oncogene in multiple cancers and contributes to tumor progression. However, the role and biological functions of miR-17-5p in the development of laryngeal squamous cell carcinoma (LSCC) still remain unknown. METHODS: qRT-PCR was used to detect miRNA and mRNA expression levels in LSCC tissues and cell lines. CCK-8 assay was used to measure cell viability and flow cytometry was performed to evaluate cell apoptosis. Western blot analysis was used to detect the protein levels of BAX, BCL-2, cleaved Caspase-3, PIK3R1 and AKT. Luciferase reporter assay was used to detect the effect of miR-17-5p on PIK3R1 expression. Xenograft animal model was used to test the effect of miR-17-5p on LSCC cell in vivo. RESULTS: In the present study, we found that miR-17-5p expression level was upregulated in LSCC tissues and cell lines. Depletion of miR-17-5p in LSCC cells significantly reduced cell proliferation and promoted cell apoptosis in vitro and in vivo. Mechanically, knockdown of miR-17-5p in LSCC cells inhibited BCL-2 expression while enhanced BAX and cleaved Caspase-3 protein expression. Moreover, depletion of miR-17-5p in LSCC cells suppressed AKT phosphorylation but did not influence PTEN expression. Importantly, miR-17-5p positively regulated PIK3R1 expression by directly binding to its 3'-untranslated region (UTR). Additionally, PIK3R1, which expression was downregulated in LSCC tissues and cell lines, was involved in LSCC cell survival by modulating the activation of AKT signal pathway. Dysregulation of miR-17-5p/PIK3R1 axis was participated in LSCC cell proliferation and apoptosis by inhibiting the activation of the PI3K/AKT signaling pathway. CONCLUSIONS: In conclusion, our study indicates that the miR-17-5p/PIK3R1 axis plays an essential role in the development of LSCC and provides a potential therapeutic target for LSCC treatment. CI - (c) The Author(s) 2020. FAU - Wang, Jian-Xing AU - Wang JX AD - 1Department of Otolaryngology, The Second Hospital of Hebei Medical University, 215 Heping West Road, Shijiazhuang, 050000 People's Republic of China. ISNI: 0000 0004 1804 3009. GRID: grid.452702.6 FAU - Jia, Xin-Ju AU - Jia XJ AD - 2Department of Endocrinology, The First Hospital of Hebei Medical University, 89 Donggang Road, Shijiazhuang, 050000 People's Republic of China. GRID: grid.452458.a FAU - Liu, Yan AU - Liu Y AD - 3Department of Anesthesiology, The 4th Hospital of Hebei Medical University, 169 Tianshan Street, Shijiazhuang, 050000 People's Republic of China. ISNI: 0000 0004 1760 8442. GRID: grid.256883.2 FAU - Dong, Jin-Hui AU - Dong JH AD - 1Department of Otolaryngology, The Second Hospital of Hebei Medical University, 215 Heping West Road, Shijiazhuang, 050000 People's Republic of China. ISNI: 0000 0004 1804 3009. GRID: grid.452702.6 FAU - Ren, Xiu-Min AU - Ren XM AD - 1Department of Otolaryngology, The Second Hospital of Hebei Medical University, 215 Heping West Road, Shijiazhuang, 050000 People's Republic of China. ISNI: 0000 0004 1804 3009. GRID: grid.452702.6 FAU - Xu, Ou AU - Xu O AD - 1Department of Otolaryngology, The Second Hospital of Hebei Medical University, 215 Heping West Road, Shijiazhuang, 050000 People's Republic of China. ISNI: 0000 0004 1804 3009. GRID: grid.452702.6 FAU - Liu, Sheng-Hui AU - Liu SH AD - 4Department of Otolaryngology Head and Neck Surgery, The 4th Hospital of Hebei Medical University, 169 Tianshan Street, Shijiazhuang, 050000 People's Republic of China. ISNI: 0000 0004 1760 8442. GRID: grid.256883.2 FAU - Shan, Chun-Guang AU - Shan CG AUID- ORCID: 0000-0002-8378-5469 AD - 1Department of Otolaryngology, The Second Hospital of Hebei Medical University, 215 Heping West Road, Shijiazhuang, 050000 People's Republic of China. ISNI: 0000 0004 1804 3009. GRID: grid.452702.6 LA - eng PT - Journal Article DEP - 20200110 PL - England TA - Cancer Cell Int JT - Cancer cell international JID - 101139795 PMC - PMC6954602 OTO - NOTNLM OT - Apoptosis OT - Laryngeal squamous cell carcinoma OT - PIK3R1 OT - Proliferation OT - miR-17-5p COIS- Competing interestsThe authors declare that they have no competing interests. EDAT- 2020/01/16 06:00 MHDA- 2020/01/16 06:01 PMCR- 2020/01/10 CRDT- 2020/01/16 06:00 PHST- 2019/11/01 00:00 [received] PHST- 2020/01/02 00:00 [accepted] PHST- 2020/01/16 06:00 [entrez] PHST- 2020/01/16 06:00 [pubmed] PHST- 2020/01/16 06:01 [medline] PHST- 2020/01/10 00:00 [pmc-release] AID - 1096 [pii] AID - 10.1186/s12935-020-1096-3 [doi] PST - epublish SO - Cancer Cell Int. 2020 Jan 10;20:14. doi: 10.1186/s12935-020-1096-3. eCollection 2020.