Pin2 telomeric repeat factor 1-interacting telomerase inhibitor 1 (PinX1) inhibits nasopharyngeal cancer cell stemness: implication for cancer progression and therapeutic targeting.

Abstract

BACKGROUND:

Recurrence and distant metastasis are still the main factors leading to treatment failure for malignant tumors including nasopharyngeal carcinoma (NPC). Therefore, elucidating the molecular mechanisms underlying nasopharyngeal carcinoma metastasis is of great clinical significance for targeted gene therapy and prognostic evaluation. PinX1, a tumor suppressor gene, was previously demonstrated to be a powerful tool for targeting telomerase in order to resist malignant tumor proliferation and migration. The aim of this study was to explore the mechanism through which PinX1 regulates epithelial-mesenchymal transition (EMT) and tumor metastasis in NPC and investigate its clinical significance and biological role with respect to disease progression.

METHODS:

Cell Counting Kit-8 (CCK8), Transwell assays, Colony formation analysis and Xenograft tumorigenicity assay were used to measure the nasopharyngeal CD133+ cancer stem cell proliferation, migration, and invasion abilities. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assays were conducted to investigate the underlying mechanism that PinX1 inhibits cell proliferation, migration, and invasion via regulating EMT in nasopharyngeal CD133+ CSCs.

RESULTS:

We found that the overexpression of PinX1 and P53 inhibited cell proliferation, migration, and invasion, but that the inhibition of miR-200b blocked these effects, in nasopharyngeal CD133+ cancer stem cells (CSCs). Mechanistic investigations elucidated that PinX1 inhibits cell proliferation, migration, and invasion by regulating the P53/miR-200b-mediated transcriptional suppression of Snail1, Twist1, and Zeb1, consequently inhibiting EMT in nasopharyngeal CD133+ CSCs.

CONCLUSIONS:

Our findings indicate that PinX1 inhibits cell proliferation, migration, and invasion via P53/miR-200b-regulated EMT in the malignant progression of human NPC, which might suggest novel clinical implications for disease treatment.

• Authors: Chaosheng Yu, Fang Chen, Xiaoqi Wang, Zhimou Cai, Mengxue Yang, Qingwen Zhong, Jialian Feng, Junzheng Li, Congxiang Shen, Zhong Wen
• Journal: Journal of experimental & clinical cancer research : CR (J Exp Clin Cancer Res) Vol. 39 Issue 1 Pg. 31 (Feb 07 2020) ISSN: 1756-9966 [Electronic] England
• PMID: 32028978 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• Cell Cycle Proteins
• MicroRNAs
• PINX1 protein, human
• TP53 protein, human
• Tumor Suppressor Protein p53
• Tumor Suppressor Proteins

Topics

• Animals
• Biomarkers, Tumor
• Cell Cycle Proteins (genetics, metabolism)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Cell Transformation, Neoplastic (genetics, metabolism)
• Disease Models, Animal
• Disease Progression
• Epithelial-Mesenchymal Transition (genetics)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Mice
• MicroRNAs (genetics)
• Nasopharyngeal Neoplasms (drug therapy, genetics, pathology)
• Neoplastic Stem Cells (metabolism, pathology)
• Tumor Suppressor Protein p53 (genetics)
• Tumor Suppressor Proteins (genetics, metabolism)