Dataset Information

Knockdown of HOXA transcript at the distal tip suppresses the growth and invasion and induces apoptosis of oral tongue squamous carcinoma cells.

ABSTRACT:

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.

SUBMITTER: Mu M

PROVIDER: S-EPMC6239101 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Knockdown of HOXA transcript at the distal tip suppresses the growth and invasion and induces apoptosis of oral tongue squamous carcinoma cells.

Mu Mingkui M Li Yue Y Zhan Yuanbo Y Li Xin X Zhang Bin B

OncoTargets and therapy 20181113

<h4>Background</h4>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.<h4>Me ...[more]

PMID: 30519045

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Project description:Oral tongue squamous cell carcinoma (OTSCC) has a high mortality rate and the incidence is rising worldwide. Despite advances in treatment, the disease lacks specific prognostic markers and treatment modality. The spreading of OTSCC is dependent on the tumor microenvironment and involves tumor-associated macrophages (TAMs). Although the presence of TAMs is associated with poor prognosis in OTSCC, the specific mechanisms underlying this are still unknown. The aim here was to investigate the effect of macrophages (Mfs) on HSC-3 tongue carcinoma cells and NF-kappaB activity. We polarized THP-1 cells to M1 (inflammatory), M2 (TAM-like) and R848 (imidazoquinoline-treated) type Mfs. We then investigated the effect of Mfs on HSC-3 cell migration and NF-kappaB activity, cytokine production and invasion using several different in vitro migration models, a human 3D tissue invasion model, antibody arrays, confocal microscopy, immunohistochemistry and a mouse invasion model. We found that in co-culture studies all types of Mfs fused with HSC-3 cells, a process which was partially due to efferocytosis. HSC-3 cells induced expression of epidermal growth factor and transforming growth factor-beta in co-cultures with M2 Mfs. Direct cell-cell contact between M2 Mfs and HSC-3 cells induced migration and invasion of HSC-3 cells while M1 Mfs reduced HSC-3 cell invasion. M2 Mfs had an excess of NF-kappaB p50 subunit and a lack of p65 subunits both in the presence and absence of HSC-3 cells, indicating dysregulation and pro-tumorigenic NF-kappaB activation. TAM-like cells were abundantly present in close vicinity to carcinoma cells in OTSCC patient samples. We conclude that M2 Mfs/TAMs have an important role in OTSCC regulating adhesion, migration, invasion and cytokine production of carcinoma cells favouring tumor growth. These results demonstrate that OTSCC patients could benefit from therapies targeting TAMs, polarizing TAM-like M2 Mfs to inflammatory macrophages and modulating NF-kappaB activity.

Dataset Information

Knockdown of HOXA transcript at the distal tip suppresses the growth and invasion and induces apoptosis of oral tongue squamous carcinoma cells.

Background

Methods

Results

Conclusion

Publications

Knockdown of HOXA transcript at the distal tip suppresses the growth and invasion and induces apoptosis of oral tongue squamous carcinoma cells.

Similar Datasets

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