Knockdown of HOXA transcript at the distal tip suppresses the growth and invasion and induces apoptosis of oral tongue squamous carcinoma cells
Authors Mu M, Li Y, Zhan Y, Li X, Zhang B
Received 18 May 2018
Accepted for publication 16 August 2018
Published 13 November 2018 Volume 2018:11 Pages 8033—8044
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Cristina Weinberg
Peer reviewer comments 4
Editor who approved publication: Dr Leo Jen-Liang Su
Mingkui Mu,1 Yue Li,1 Yuanbo Zhan,2 Xin Li,3 Bin Zhang2,4
1Department of Orthodontics, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, People’s Republic of China; 2Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, People’s Republic of China; 3Department of Stomatology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, People’s Republic of China; 4Heilongjiang Academy of Medical Sciences, Harbin 150001, People’s Republic of China
Background: Oral tongue squamous cell carcinoma (OTSCC) is an aggressive cancer which has high mortality rates. HOXA transcript at the distal tip (HOTTIP) is a lncRNA that can be used as a prognostic marker in multiple carcinomas. The expression of HOTTIP is found to be elevated in OTSCC tissues, and such elevation is correlated with poor prognosis. However, its functional role in regulating the growth and metastasis of OTSCC cells remains elusive and requires further investigation.
Methods: HOTTIP-silenced OTSCC cells were established by inhibiting HOTTIP expression via its exclusive shRNA. Whether HOTTIP knockdown affected the aggressive tumor behaviors of OTSCC cells was investigated in vitro and in vivo.
Results: We found that HOTTIP shRNA restrained the cell proliferation and arrested the cell cycle at G1 phase in TSCCA and TCA8113 cells. The expression levels of cyclins B, D1, and E were downregulated in HOTTIP-silenced cells. HOTTIP silencing suppressed the growth of xenograft tumors. Moreover, the silencing of HOTTIP triggered apoptosis in TSCCA and TCA8113 cells and altered the expression of a group of apoptosis-related molecules: downregulated Bcl-2, upregulated Bax, and enhanced the cleavage of caspase 3 and PARP. Knockdown of HOTTIP also suppressed the migration, invasion, and epithelial–mesenchymal transition (EMT) of both TSCCA and TCA8113 cell lines.
Conclusion: Our findings suggest that HOTTIP is required by the OTSCC cells to maintain their growth and metastasis in vitro. It may serve as a promising potential candidate for OTSCC therapy.
Keywords: HOTTIP, oral tongue squamous cell carcinoma, proliferation, metastasis, apoptosis, tumorigenicity
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