PMID- 27035337 OWN - NLM STAT- MEDLINE DCOM- 20170221 LR - 20220409 IS - 1791-3004 (Electronic) IS - 1791-2997 (Linking) VI - 13 IP - 5 DP - 2016 May TI - Co‑inhibition of miRNA‑21 and miRNA‑221 induces apoptosis by enhancing the p53‑mediated expression of pro‑apoptotic miRNAs in laryngeal squamous cell carcinoma. PG - 4315-20 LID - 10.3892/mmr.2016.5048 [doi] AB - Dysregulation of a numerous microRNAs (miRNAs) has been implicated in laryngeal squamous cell carcinoma (LSCC). Among those miRNAs, miR‑21 and miR‑221 are co‑overexpressed and commonly target the phosphatase and tensin homolog protein (PTEN) that is located in the PTEN‑Akt signaling pathway. The present study investigated whether co‑inhibition of miR‑21 and miR‑221 induced synergistic apoptosis of human LSCC cells. Methyl thiazolyl tetrazolium (MTT) and terminal deoxynucleotidyl‑transferase‑mediated deoxynucleotide triphosphate nick end labeling (TUNEL) assays were used to observe the potential effect of miR‑21 and miR‑221 on cell viability and apoptosis in cells co‑transfected with anti‑miRNA oligonucleotide (AMO)‑21 and AMO‑221. The protein expression levels of PTEN, Akt and p53 were determined by western blotting. The cellular abundance of 6 pro‑apoptotic miRNAs transcribed by p53 mediation, consisting of miR‑15a, miR‑16‑1, miR‑26a, miR‑34a, miR‑143 and miR‑203, was measured with using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). MTT results indicate that in vitro co‑transfection of AMO‑21 and AMO‑221 leads to a decline in cell viability, compared with the transfection of AMO alone. This result was verified by the detection of apoptosis using TUNEL assays. Co‑transfection of AMO‑21 and AMO‑221 resulted in a marked reduction in Akt phosphorylation and enhanced expression of PTEN and p53 were observed; consequently, leading to an amplification of the transcription of 6 pro‑apoptotic miRNAs. The present findings confirmed that co‑inhibition of miR‑21 and miR‑221 synergistically triggers cell apoptosis in vitro. The altered PTEN‑Akt signaling and p53‑mediated amplification of the transcription of pro‑apoptotic miRNAs may be involved in the observed synergistic effect. The present study provides novel insights into the mechanism underlying apoptosis‑associated miRNA‑miRNA mutual regulation in LSCC. FAU - Kan, Xuan AU - Kan X AD - Department of Otolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China. FAU - Sun, Yanan AU - Sun Y AD - Department of Otolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China. FAU - Lu, Jianguang AU - Lu J AD - Department of Otolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China. FAU - Li, Minghua AU - Li M AD - Department of Otolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China. FAU - Wang, Yu AU - Wang Y AD - Department of Otolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China. FAU - Li, Qiuying AU - Li Q AD - Department of Otolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China. FAU - Liu, Ying AU - Liu Y AD - Department of Otolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China. FAU - Liu, Ming AU - Liu M AD - Department of Otolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China. FAU - Tian, Linli AU - Tian L AD - Department of Otolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China. LA - eng PT - Journal Article DEP - 20160328 PL - Greece TA - Mol Med Rep JT - Molecular medicine reports JID - 101475259 RN - 0 (MIRN21 microRNA, human) RN - 0 (MIRN221 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Neoplasm) RN - 0 (TP53 protein, human) RN - 0 (Tumor Suppressor Protein p53) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 3.1.3.67 (PTEN Phosphohydrolase) RN - EC 3.1.3.67 (PTEN protein, human) SB - IM MH - *Apoptosis MH - Carcinoma, Squamous Cell MH - *Gene Expression Regulation, Neoplastic MH - Hep G2 Cells MH - Humans MH - Laryngeal Neoplasms MH - MicroRNAs/*antagonists & inhibitors/biosynthesis/genetics MH - PTEN Phosphohydrolase/genetics/metabolism MH - Proto-Oncogene Proteins c-akt/genetics/metabolism MH - RNA, Neoplasm/*antagonists & inhibitors/biosynthesis/genetics MH - *Signal Transduction MH - Tumor Suppressor Protein p53/*biosynthesis/genetics EDAT- 2016/04/02 06:00 MHDA- 2017/02/22 06:00 CRDT- 2016/04/02 06:00 PHST- 2015/03/18 00:00 [received] PHST- 2016/03/03 00:00 [accepted] PHST- 2016/04/02 06:00 [entrez] PHST- 2016/04/02 06:00 [pubmed] PHST- 2017/02/22 06:00 [medline] AID - 10.3892/mmr.2016.5048 [doi] PST - ppublish SO - Mol Med Rep. 2016 May;13(5):4315-20. doi: 10.3892/mmr.2016.5048. Epub 2016 Mar 28.