PTTG1 regulated by miR-146a-3p promotes bladder cancer migration, invasion, metastasis and growth

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.

The long non-coding RNA PTTG3P promotes cell growth and metastasis via up-regulating PTTG1 and activating PI3K/AKT signaling in hepatocellular carcinoma

“…PTTG1 was reported to be up-regulated in various cancers [ 43 ]. Overexpression of PTTG1 can promote cell proliferation, inhibit cell apoptosis and induce EMT [ 44 , 45 ]. Moreover, PTTG1 has been demonstrated to activate PI3K/AKT signaling [ 46 ].…”

Targeting the PTTG1 oncogene impairs proliferation and invasiveness of melanoma cells sensitive or with acquired resistance to the BRAF inhibitor dabrafenib

“…PTTG1 is considered an oncogene [ 5 , 6 ], and it is over-expressed in a variety of cancer cell lines as well as in a wide range of primary and metastatic tumors [ 1 – 4 , 7 – 12 ], including melanoma [ 13 ]. Notably, PTTG1 is one of the 17 gene-expression signature predicting metastasis and shorter survival in multiple tumor types [ 14 ] and it is among the top-20 genes whose elevated expression was found to be associated with metastatic dissemination of melanoma [ 15 , 16 ].…”

“…Notably, PTTG1 is one of the 17 gene-expression signature predicting metastasis and shorter survival in multiple tumor types [ 14 ] and it is among the top-20 genes whose elevated expression was found to be associated with metastatic dissemination of melanoma [ 15 , 16 ]. The involvement of PTTG1 in tumor growth and metastasis is further highlighted by several studies showing that in cancer cell lines of various histological derivation ectopic expression of PTTG1 enhanced proliferation and/or invasiveness, whereas PTTG1 silencing produced opposite results [ 7 , 8 , 10 – 12 , 17 – 22 ].…”

Effect and mechanism of miR‑146a on malignant biological behaviors of lung adenocarcinoma cell line

“…miR-146a plays important roles in the development and progression of many types of tumors, and it has been widely studied and reported in recent years. The expression of miR-146a is decreased significantly in breast (26,27), liver (28,29), prostate (30) and bladder cancer (31), and upregulation of miR-146a can inhibit the proliferation, invasion, and metastasis of these tumor cells and promote apoptosis (26-31); Figure 6. Detection of miR-146a targeted genes using a dual-luciferase reporter assay system.…”