title: Let-7d functions as novel regulator of epithelial-mesenchymal transition and chemoresistant property in oral cancer.
abstract: Oral squamous cell carcinoma (OSCC) is a prevalent cancer worldwide. Let-7 family has been shown to function as a tumor suppressor through regulating multiple oncogenic signaling. Recent study reported that combined underexpression of miR-205 and let-7d showed negative correlation with the survival prognosis of head and neck cancer patients. However, the let-7d-involved mechanism in regulating OSCC is still unclear. In this study, we first demonstrated that let-7d expression was significantly decreased while Twist and Snail expression was increased in OSCC cancer cell lines and primary cultures as compared to normal human oral keratinocyte cells. To further investigate the role of let-7d in OSCC, we applied the SPONGE method to knock down let-7d in OECM-1 and two primary OSCC cell types. The results showed that knockdown of let-7d promote epithelial-mesenchymal transition (EMT) traits and migratory/invasive capabilities in OSCC cells. Furthermore, down-expression of let-7d significantly activated Twist and Snail expressions and chemo-resistant abilities of OSCC cells. Notably, overexpression of let-7d effectively reversed the EMT phenotype, blocked migratory/invasive abilities, and further increased the chemosensitivity in oral cancer tumor initiating ALDH1+ cells. In sum, these results show that let-7d negatively modulates EMT expression and also plays a role in regulating chemo-resistant ability in oral cancer.
authors: Department of Pharmacy Practice, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan, ROC.
authors: Charn-Jung
authors: CJ
authors: Chang
authors: Chuan-Chih
authors: CC
authors: Hsu
authors: Chin-Hong
authors: CH
authors: Chang
authors: Lo-Lin
authors: LL
authors: Tsai
authors: Yu-Chao
authors: YC
authors: Chang
authors: Shao-Wei
authors: SW
authors: Lu
authors: Cuuan-Hang
authors: CH
authors: Yu
authors: Hsu-Shan
authors: HS
authors: Huang
authors: Jhi-Joung
authors: JJ
authors: Wang
authors: Chung-Hung
authors: CH
authors: Tsai
authors: Ming-Yung
authors: MY
authors: Chou
authors: Cheng-Chia
authors: CC
authors: Yu
authors: Fang-Wei
authors: FW
authors: Hu
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000096:biosynthesis; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis; D014162:Transfection; D051879:Twist-Related Protein 1 / Q000096:biosynthesis
chemical_list: D035683:MicroRNAs; D009687:Nuclear Proteins; D000071250:Snail Family Transcription Factors; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1; C487931:mirnlet7 microRNA, human