Silencing novel long non-coding RNA FKBP9P1 represses malignant progression and inhibits PI3K/AKT signaling of head and neck squamous cell carcinoma in vitro.

BACKGROUND

Long non-coding RNAs (lncRNAs) play key roles in human cancers. In our previous study, we demonstrated that lncRNA FKBP prolyl isomerase 9 pseudogene 1 (FKBP9P1) was highly expressed in head and neck squamous cell cancer (HNSCC) tissues. However, its functional significance remains poorly understood. In the present study, we identify the role and potential molecular biologic mechanisms of FKBP9P1 in HNSCC.

METHODS

Quantitative real-time polymerase chain reaction was used to detect the expression of FKBP9P1 in HNSCC tissues, matched adjacent normal tissues, human HNSCC cells (FaDu, Cal-27, SCC4, and SCC9), and human immortalized keratinocytes cell HaCaT (normal control). Cal-27 and SCC9 cells were transfected with sh-FKBP9P1-1, sh-FKBP9P1-2, and normal control (sh-NC) lentivirus. Cell counting kit-8 assay, colony formation assay, wound healing assay, and trans-well assay were used to explore the biologic function of FKBP9P1 in HNSCC cells. Furthermore, western blotting was used to determine the mechanism of FKBP9P1 in HNSCC progression. Chi-squared test was performed to assess the clinical significance among FKBP9P1 high-expression and low-expression groups. Survival analyses were performed using the Kaplan-Meier method and assessed using the log-rank test. The comparison between two groups was analyzed by Student t test, and comparisons among multiple samples were performed by one-way analysis of variance and a Bonferroni post hoc test.

RESULTS

FKBP9P1 expression was significantly up-regulated in HNSCC tissues (tumor vs. normal, 1.914 vs. 0.957, t = 7.746, P < 0.001) and cell lines (P < 0.01 in all HNSCC cell lines). Besides, the median FKBP9P1 expression of HNSCC tissues (1.677) was considered as the threshold. High FKBP9P1 level was correlated with advanced T stage (P = 0.022), advanced N stage (P = 0.036), advanced clinical stage (P = 0.018), and poor prognosis of HNSCC patients (overall survival, P = 0.002 and disease-free survival, P < 0.001). Knockdown of FKBP9P1 led to marked repression in proliferation, migration, and invasion of HNSCC cells in vitro (P all < 0.01). Mechanistically, silencing FKBP9P1 was observed to restrain the PI3K/AKT signaling pathway.

CONCLUSIONS

Silencing lncRNA FKBP9P1 represses HNSCC progression and inhibits PI3K/AKT (phosphatidylinositol 3 kinase/AKT Serine/Threonine Kinase) signaling in vitro. Therefore, FKBP9P1 could be a potential new target for the diagnosis and treatment of HNSCC patients.