PMID- 26617795 OWN - NLM STAT- MEDLINE DCOM- 20160926 LR - 20211203 IS - 1936-2625 (Electronic) IS - 1936-2625 (Linking) VI - 8 IP - 9 DP - 2015 TI - TMP21 modulates cell growth in papillary thyroid cancer cells by inducing autophagy through activation of the AMPK/mTOR pathway. PG - 10824-31 AB - OBJECTIVE: To investigate the role of transmembrane protein (TMP) 21 in human thyroid cancer. METHODS: The recombinant expression vector pcDNA3.1 (+)-TMP21 and specific small interfering RNAs (siRNA) against TMP21 were transfected into a papillary thyroid cancer cell line (TPC1). After transfection, the expression of TMP21 was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Moreover, cell viability and apoptosis rate were respectively determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) colorimetric assay and flow cytometry (FCM). Additionally, Western blotting was performed to analyze the adenosine monophosphate (AMP)-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathways associated protein (P-AMPKalpha(Thr172), P-mTOR(Ser2448), light chain (LC)-II/LC3-I, and P-S6K(Thr389)) after pre-treatment with AMPK inhibitor, compound C (Com C) and siTMP21. RESULTS: The TMP21 protein level and cell viability were significantly higher, but apoptotic rate was significantly lower by transfection with pcDNA3.1-TMP21 than those in control group (P < 0.05), and reverse results were obtained by transfection with siTMP21. However, qRT-PCR showed different results due to the feedback inhibition of mRNA. Besides, silencing of TMP21 significantly reduced the levels of P-mTOR(Ser2448) and P-S6K(Thr389) (P < 0.05), but significantly increased the levels of P-AMPKalpha(Thr172) and LC3-II/LC3-I compared with the control group (P < 0.01). Whereas, the levels of P-AMPKalpha(Thr172) and LC3-II/LC3-I were significantly decreased by Com C compared with the control group (P < 0.05). CONCLUSION: TMP21 modulates cell growth in TPC1 cells by inducing autophagy, which may be associated with activation of AMPK/mTOR pathway. FAU - Xu, Xiaobo AU - Xu X AD - Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine Shanghai 200011, China. FAU - Gao, Hongqiang AU - Gao H AD - Department of General Surgery, Shanghai Fengcheng Hospital Shanghai 201411, China. FAU - Qin, Jian AU - Qin J AD - Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine Shanghai 200011, China. FAU - He, Liu AU - He L AD - Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine Shanghai 200011, China. FAU - Liu, Wenyong AU - Liu W AD - Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine Shanghai 200011, China. LA - eng PT - Journal Article DEP - 20150901 PL - United States TA - Int J Clin Exp Pathol JT - International journal of clinical and experimental pathology JID - 101480565 RN - 0 (Membrane Proteins) RN - 0 (Nucleocytoplasmic Transport Proteins) RN - 0 (Protein Kinase Inhibitors) RN - 0 (TMED10 protein, human) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) SB - IM MH - AMP-Activated Protein Kinases/antagonists & inhibitors/*metabolism MH - Apoptosis MH - *Autophagy/drug effects MH - Carcinoma/*enzymology/genetics/pathology MH - Carcinoma, Papillary MH - Cell Line, Tumor MH - *Cell Proliferation/drug effects MH - Cell Survival MH - Enzyme Activation MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Membrane Proteins/genetics/*metabolism MH - Nucleocytoplasmic Transport Proteins MH - Phosphorylation MH - Protein Kinase Inhibitors/pharmacology MH - RNA Interference MH - Signal Transduction MH - TOR Serine-Threonine Kinases/*metabolism MH - Thyroid Cancer, Papillary MH - Thyroid Neoplasms/*enzymology/genetics/pathology MH - Time Factors MH - Transfection PMC - PMC4637610 OTO - NOTNLM OT - AMPK/mTOR OT - Thyroid cancer OT - autophagy OT - transmembrane protein 21 EDAT- 2015/12/01 06:00 MHDA- 2016/09/27 06:00 PMCR- 2015/09/01 CRDT- 2015/12/01 06:00 PHST- 2015/05/25 00:00 [received] PHST- 2015/06/29 00:00 [accepted] PHST- 2015/12/01 06:00 [entrez] PHST- 2015/12/01 06:00 [pubmed] PHST- 2016/09/27 06:00 [medline] PHST- 2015/09/01 00:00 [pmc-release] PST - epublish SO - Int J Clin Exp Pathol. 2015 Sep 1;8(9):10824-31. eCollection 2015.