PMID- 28819440
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1837-9664 (Print)
IS  - 1837-9664 (Electronic)
IS  - 1837-9664 (Linking)
VI  - 8
IP  - 12
DP  - 2017
TI  - MicroRNA-204-5p inhibits invasion and metastasis of laryngeal squamous cell 
      carcinoma by suppressing forkhead box C1.
PG  - 2356-2368
LID - 10.7150/jca.19470 [doi]
AB  - Background and aim: Understanding the molecular biological mechanisms underlying 
      laryngeal squamous cell carcinoma (LSCC) invasion and metastasis is crucial for 
      diagnosis, treatment, and prognosis. We aimed to examine the expression of the 
      tumor suppressor microRNA-204-5p (miR-204-5p) and its target gene, forkhead box 
      C1 (FOXC1), in human LSCC and explore their roles in the malignant behaviors of 
      LSCC Hep-2 and TU-177 cells. Methods: The regulatory effects of miR-204-5p on the 
      3' untranslated region of FOXC1 predicted by bioinformatics were tested by 
      dual-luciferase reporter assay. Quantitative RT-PCR was used to detect mRNA 
      expression in 43 fresh samples of LSCC and corresponding adjacent normal mucosa 
      (ANM). FOXC1 protein expression was examined by immunohistochemistry. miR-204-5p 
      mimics and FOXC1 siRNA were transfected into LSCC cell lines Hep-2 and TU-177 to 
      observe malignant behavior. miR-204-5p mimics were injected into Hep-2 or TU-177 
      xenograft tumors in nude mice to examine tumor growth.Results: The miR-204-5p 
      mRNA level was lower in all 43 LSCC samples than in the ANM samples, but the 
      FOXC1 level was higher in the LSCC samples than in the ANM samples. The 
      miR-204-5p level was lower for stage III and IV cancer and lymph node N+ status 
      samples than for stage I and II cancer and N0 status samples. FOXC1 mRNA and 
      protein levels were higher for N+ than for N0 LSCC. The miR-204-5p mRNA levels 
      were lower in Hep-2 and TU-177 cells than in ANM tissues, but FOXC1 mRNA levels 
      were higher in Hep-2 and TU-177 cells than in ANM tissues. Dual-luciferase 
      reporter assays demonstrated the targeted regulatory effects of miR-204-5p on the 
      FOXC1 3' UTR. Cell proliferation and colony formation was facilitated with 
      miR-204-5p mimics and FOXC1 siRNA, with weaker cell migration and invasion than 
      the controls. Moreover, miR-204-5p overexpression or FOXC1 knockdown inhibited 
      the EMT process in LSCC cells. In vivo experiments demonstrated that injection of 
      miR-204-5p into Hep-2 and TU-177 xenograft tumors in nude mice significantly 
      inhibited tumor growth. Conclusions: miR-204-5p is involved in the invasion and 
      metastasis of LSCC. It has a targeted regulatory effect on FOXC1 expression; 
      malignant LSCC behaviors, including cell proliferation, invasion, and metastasis, 
      are suppressed, and tumor growth in vivo is inhibited. This suggests that 
      miR-204-5p may be a target for molecular therapy of LSCC in the future.
FAU - Gao, Wei
AU  - Gao W
AD  - Department of Otolaryngology, Head & Neck Surgery, The First Hospital, Shanxi 
      Medical University, Taiyuan, Shanxi, China.
AD  - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan, 
      Shanxi, China.
FAU - Wu, Yongyan
AU  - Wu Y
AD  - Department of Otolaryngology, Head & Neck Surgery, The First Hospital, Shanxi 
      Medical University, Taiyuan, Shanxi, China.
AD  - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan, 
      Shanxi, China.
FAU - He, Xiaoling
AU  - He X
AD  - Department of Otolaryngology, Head & Neck Surgery, The First Hospital, Shanxi 
      Medical University, Taiyuan, Shanxi, China.
FAU - Zhang, Chunming
AU  - Zhang C
AD  - Department of Otolaryngology, Head & Neck Surgery, The First Hospital, Shanxi 
      Medical University, Taiyuan, Shanxi, China.
AD  - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan, 
      Shanxi, China.
FAU - Zhu, Meixia
AU  - Zhu M
AD  - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan, 
      Shanxi, China.
FAU - Chen, Bo
AU  - Chen B
AD  - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan, 
      Shanxi, China.
FAU - Liu, Qingqing
AU  - Liu Q
AD  - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan, 
      Shanxi, China.
FAU - Qu, Xukuan
AU  - Qu X
AD  - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan, 
      Shanxi, China.
FAU - Li, Weiyan
AU  - Li W
AD  - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan, 
      Shanxi, China.
FAU - Wen, Shuxin
AU  - Wen S
AD  - Department of Otolaryngology, Head & Neck Surgery, The First Hospital, Shanxi 
      Medical University, Taiyuan, Shanxi, China.
AD  - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan, 
      Shanxi, China.
FAU - Wang, Binquan
AU  - Wang B
AD  - Department of Otolaryngology, Head & Neck Surgery, The First Hospital, Shanxi 
      Medical University, Taiyuan, Shanxi, China.
AD  - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan, 
      Shanxi, China.
LA  - eng
PT  - Journal Article
DEP - 20170721
PL  - Australia
TA  - J Cancer
JT  - Journal of Cancer
JID - 101535920
PMC - PMC5560155
OTO - NOTNLM
OT  - FOXC1
OT  - hsa-miR-204-5p
OT  - invasion
OT  - laryngeal squamous cell carcinoma
OT  - metastasis
COIS- Competing Interests: The authors declare no conflict of interest.
EDAT- 2017/08/19 06:00
MHDA- 2017/08/19 06:01
PMCR- 2017/01/01
CRDT- 2017/08/19 06:00
PHST- 2017/02/03 00:00 [received]
PHST- 2017/05/10 00:00 [accepted]
PHST- 2017/08/19 06:00 [entrez]
PHST- 2017/08/19 06:00 [pubmed]
PHST- 2017/08/19 06:01 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - jcav08p2356 [pii]
AID - 10.7150/jca.19470 [doi]
PST - epublish
SO  - J Cancer. 2017 Jul 21;8(12):2356-2368. doi: 10.7150/jca.19470. eCollection 2017.