Knockdown of PNO1 inhibits esophageal cancer progression

Abstract

The present study aimed to investigate the role of partner of NOB1 homolog (PNO1) in esophageal cancer (EC). The expression levels of PNO1 in EC were primarily analyzed using data obtained from databases. PNO1 expression was also knocked down in EC cells (Eca-109 and TE1) to determine the biological effects of PNO1 on tumorigenesis in vitro and in vivo. In addition, possible downstream targets of PNO1 in EC were identified. The expression levels of PNO1 were upregulated in the tumor tissues compared with that noted in normal tissues. Moreover, the knockdown (KD) of PNO1 suppressed cell proliferation, migration and invasion, and promoted cell apoptosis (P<0.05). Furthermore, the protein expression levels of AKT1, Twist, Myc, mTOR, matrix metalloproteinase 2 (MMP2), nuclear factor (NF)-κB p65 and β-catenin 1 (CTNNB1) were downregulated following the KD of PNO1 in Eca-109 cells (P<0.05). In addition, the overexpression of CTNNB1 reversed the effects of PNO1 KD in Eca-109 cells (P<0.05). In conclusion, the findings of the present study suggest that PNO1 promotes EC progression by regulating AKT1, Twist, Myc, mTOR, MMP2, NF-κB p65 and CTNNB1 expression.Construction of stable PNO1-knockdown (KD) and β-catenin (CTNNB1)-overexpressing cells. PNO1 was stably knocked down in Eca-109 and TE-1 cells using short hairpin RNA (sh), and CTNNB1 was stably overexpressed in Eca-109 cells only. sh-PNO1-KD, sh-PNO1-negative control (NC), sh-CTNNB1-OE and sh-CTNNB1-negative control (NC)

Inhibition of ribosome assembly factor PNO1 by CRISPR/Cas9 technique suppresses lung adenocarcinoma and Notch pathway: Clinical application

“…In the present study, PNO1 was overexpressed in lung adenocarcinoma, and its inhibition by CRISPR/Cas9 technology inhibited cell proliferation, motility, migration, and invasion, and induced apoptosis. Our data are in agreement with others where PNO1 has been shown to promote cell proliferation and migration, and PNO1 knockdown inhibited tumorigenesis 7,8,10,11,38 . These data suggest that PNO1 can be used as a diagnostic and prognostic biomarker for lung cancer, and its inhibition can be used for the treatment of cancer.…”

“…Our data are in agreement with others where PNO1 has been shown to promote cell proliferation and migration, and PNO1 knockdown inhibited tumorigenesis. 7,8,10,11,38 These data suggest that PNO1 can be used as a diagnostic and prognostic biomarker for lung cancer, and its inhibition can be used for the treatment of cancer.…”

“…Cancer cells rely on ribosome biogenesis which increases in cancer cells to cope with a rise in protein synthesis and sustain unrestricted growth 53,54 . The oncogenic role of PNO1 in cancer has recently been reported 7–9,11,38,55 . In hepatocellular carcinoma, celecoxib inhibited PNO1 expression and tumour growth through modulation of AKT/mTOR signalling pathway 7 .…”

“… 53 , 54 The oncogenic role of PNO1 in cancer has recently been reported. 7 , 8 , 9 , 11 , 38 , 55 In hepatocellular carcinoma, celecoxib inhibited PNO1 expression and tumour growth through modulation of AKT/mTOR signalling pathway. 7 In colorectal cancer, EBF1 over‐expression down‐regulated PNO1 expression and transcription, and up‐regulated the expression of p53 and p21 proteins.…”

“… 6 In spite of its role in ribosome biogenesis, the mechanism by which PNO1 regulates oncogenesis is not well understood. Since PNO1 is highly expressed in cancer cells, 7 , 8 , 9 , 10 , 11 it can be used as a diagnostic biomarker and also can be an attractive target for cancer therapy. Therefore, understanding the expression and biological function of PNO1 is crucial for effectively managing lung adenocarcinoma.…”