Abstract
Pituitary tumor-transforming gene 1 (PTTG1) is identified as an oncogene, and overexpresses in many tumors. However, the role of PTTG1 in bladder cancer (BC) hasn't yet been characterized well. In this study, we showed the expression of PTTG1 mRNA and protein were both significantly increased in BC tissues and cells. The PTTG1 protein levels were positive correlated with increased tumor size, tumor–node–metastasis (TNM) stage, lymphatic invasion and distant metastasis of BC. PTTG1 knockdown dramatically suppressed the migration, invasion, metastasis and growth, and induced senescence and cell-cycle arrest at G0/G1 phase of BC cells. We further identified PTTG1 was the direct target of miR-146a-3p through using target prediction algorithms and luciferase reporter assay. miR-146a-3p was low expressed and negatively correlated with PTTG1 levels in BC tissues and cells. miR-146a-3p overexpression inhibited migration, invasion, metastasis and growth, and induced senescence of BC cells. Rescue experiment suggested ectopic expression of miR-146a-3p and PTTG1 suppressed migration, invasion and induced cell cycle arrest and senescence of BC cells compared to PTTG1 overexpression, confirming miR-146a-3p inhibited BC progression by targeting PTTG1. In summary, our study found miR-146a-3p/PTTG1 axis regulated BC migration, invasion, metastasis and growth, and might be a targets for BC therapy.
Highlights
bladder cancer (BC) is a common malignancy and the second most lethal type of tumor among individuals with genitourinary cancer in the west world [1]
Real-time RT-PCR suggested Pituitary tumor-transforming gene 1 (PTTG1) was significantly upregulated in bladder cancer tissues compared to adjacent normal bladder tissues (Figure 1C)
We analyzed the correlation between PTTG1 expression and some clinical parameters, such as gender, age, tumor size, histologic grade, tumor– node–metastasis (TNM) stage, lymphatic invasion and distant metastasis, and found increased PTTG1 expression was correlated with tumor size, TNM stage, lymphatic invasion and distant metastasis, but there was no significant correlation between PTTG1 with other clinical pathologic characteristics including gender, age, or histologic grade in BC (Table 1)
Summary
BC is a common malignancy and the second most lethal type of tumor among individuals with genitourinary cancer in the west world [1]. PTTG1 which resides at human chromosome 5q33.3 and encodes a securin protein, is first isolated from rat pituitary tumor cells in 1997 [3]. PTTG1 was subsequently demonstrated to be abundantly expressed in several types of human malignancies, such as pituitary, pulmonary, pancreatic, renal, prostatic and colorectal cancers [6,7,8,9,10,11]. Previous studies indicated that PTTG1 is involved in the modulation of metastasis in human ovarian cancer [12], and is implicated in the regulation of senescence and growth of pituitary tumor [13]. The mechanisms www.impactjournals.com/oncotarget underlying the regulation and the downstream signaling pathway of PTTG1 in various cancer cells remain largely unknown
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