title: Loss of SNAIL inhibits cellular growth and metabolism through the miR-128-mediated RPS6KB1/HIF-1α/PKM2 signaling pathway in prostate cancer cells.
abstract: SNAIL is a promising target for the treatment of cancer because it is known to promote epithelial-mesenchymal transition. Recent studies suggest that SNAIL also takes part in metabolic reprogramming and chemotherapy resistance in some cancers. In prostate cancer (PCa), SNAIL has been proved to be required for hypoxia-induced invasion and as a potential marker for predicting the recurrence. However, the role of SNAIL in PCa aberrant metabolism is poorly understood. In this study, we identified that SNAIL regulated cellular growth and energy metabolism through the miR-128-mediated ribosomal protein S6 kinase 1 (RPS6KB1)/HIF-1α/PKM2 signaling pathway which played a key role in the reprogramming of cancer metabolism. Using quantitative RT-PCR (qRT-PCR), we found that SNAIL expression was elevated in castration-resistant prostate cancer tissues compared with androgen-dependent prostate cancer tissues and nontumorous tissues. Depletion of SNAIL increased miR-128 expression levels, inhibited cell growth, reduced glucose consumption and lactate production, and repressed the expression of RPS6KB1, HIF-1α, and PKM2 in PCa cells. Luciferase reporter assays showed the SNAIL regulated miR-128 expression at the transcriptional level and miR-128 modulated RPS6KB1 expression at the translational level. Furthermore, down-expression of miR-128 partially restored the effect of si-SNAIL on the suppression of cellular growth, metabolism, and RPS6KB1/HIF-1α/PKM2 signaling pathway. To our knowledge, it is the first time to demonstrate that SNAIL/miR-128/RPS6KB1 pathway plays a critical role in the progression of PCa.
authors.affiliation: Department of Urology, Zhongda Hospital, Medical School, Southeast University, 87 Ding jia Bridge Hunan Road, Nanjing, 210009, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Tao
authors.forename: Guifang
authors.initials: G
authors.lastname: Li
authors.forename: Qingsheng
authors.initials: Q
authors.lastname: Dong
authors.forename: Dachuang
authors.initials: D
authors.lastname: Liu
authors.forename: Chunhui
authors.initials: C
authors.lastname: Liu
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Han
authors.forename: Yeqing
authors.initials: Y
authors.lastname: Huang
authors.forename: Shuqiu
authors.initials: S
authors.lastname: Chen
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014176:Protein Biosynthesis; D011770:Pyruvate Kinase / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C545189:MIRN128 microRNA, human; D035683:MicroRNAs; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D008156:Luciferases; D011770:Pyruvate Kinase; D038762:Ribosomal Protein S6 Kinases, 70-kDa; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1; D005947:Glucose