Abstract
Lung cancer is the leading cause of cancer-related mortality worldwide. PEST-containing nuclear protein (PCNP) has been found in the nucleus of cancer cells. Whether PCNP plays a role in the growth of lung adenocarcinoma is still unknown. In the present study, the results indicated that the level of PCNP in lung adenocarcinoma tissue was significantly higher than that in corresponding adjacent non-tumor tissue. Over-expression of PCNP promoted the proliferation, migration, and invasion of lung adenocarcinoma cells, while down-regulation of PCNP exhibited opposite effects. PCNP over-expression decreased apoptosis through up-regulating the expression levels of phospho (p)-signal transducers and activators of transcription (STAT) 3 and p-STAT5 in lung adenocarcinoma cells, whereas PCNP knockdown showed opposite trends. PCNP overexpression enhanced autophagy by increasing the expression levels of p-phosphatidylinositol 3-kinase (PI3K), p-Akt, and p-mammalian target of rapamycin (mTOR) in lung adenocarcinoma cells, however an opposite trend was observed in the sh-PCNP group. In addition, overexpression of PCNP showed the tumor-promoting effect on xenografted lung adenocarcinoma, while PCNP knockdown reduced the growth of lung adenocarcinoma via regulating angiogenesis. Our study elucidates that PCNP can regulate the procession of human lung adenocarcinoma cells via STAT3/5 and PI3K/Akt/mTOR signaling pathways. PCNP may be considered as a promising biomarker for the diagnosis and prognosis in patients with lung adenocarcinoma. Furthermore, PCNP can be a novel therapeutic target and potent PCNP inhibitors can be designed and developed in the treatment of lung adenocarcinoma.
Highlights
Lung cancer is the leading cause of cancer-related death in the world[1,2]
PEST-containing nuclear protein (PCNP) protein level is higher in human lung adenocarcinoma tissue than that in adjacent normal tissue In light of the fact that lung adenocarcinoma is the major form of lung cancer, lung adenocarcinoma was investigated in the present study
The results indicate that PCNP may be a promising biomarker for diagnosis and prognosis of lung adenocarcinoma and can serve as a growth regulator in lung adenocarcinoma cells
Summary
Lung cancer is the leading cause of cancer-related death in the world[1,2]. Lung cancer can be divided into many histological categories, including lung adenocarcinoma, large cell carcinoma, squamous cell lung carcinoma, and small cell lung carcinoma[3]. The majority of patients with lung cancer present with locally advanced/metastatic. (EGFR) tyrosine kinase domain have been found in NSCLC10,11. EGFR tyrosine kinase inhibitors (TKIs) are regarded as the standard first-line treatment of patients with advanced/recurrent NSCLC harboring activating EGFR mutations[10,12,13]. Patients treated with EGFR-TKIs can develop resistance against these drugs[10,12]. Identification of specific molecular targets and development of effective therapeutic strategies are still urgently needed for the treatment of lung cancer[2,4,14]
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