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LINC-PINT plays an anti-tumor role in nasopharyngeal carcinoma by binding to XRCC6 and affecting its function.
- Source :
-
Pathology, research and practice [Pathol Res Pract] 2024 Aug; Vol. 260, pp. 155460. Date of Electronic Publication: 2024 Jul 18. - Publication Year :
- 2024
-
Abstract
- Background: LINC-PINT was downregulated in nasopharyngeal carcinoma (NPC) and correlated with treatment efficiency of NPC. However, the underlying mechanism of LINC-PINT in NPC has not yet been fully explored.<br />Method: We used CellTiter luminescent assay, clone formation assay, Hoechst staining, and SYTO-9/PI staining to examine cell viability and cell apoptosis regulated by LINC-PINT in NPC cells. Xenograft tumor model, HE staining, Ki67 staining, and TUNEL assay were conducted to assess the role of LINC-PINT in vivo. Bioinformatics and RNA immunoprecipitation assay was performed to identify the binding protein of LINC-PINT. Fluorescence in situ hybridization and immunofluorescence were utilized to measure the colocalization of XRCC6 with LINC-PINT and DNA-PKcs. Mito-Tracker red CMXRos staining was used to label mitochondria in cells specifically.<br />Result: We found LINC-PINT was downregulated in many tumors (including NPC) and associated with poor prognosis. The cell viability was significantly inhibited and cell apoptosis was remarkably promoted in LINC-PINT overexpressed cells in contrast to control cells. The growth of tumor xenografts was significantly suppressed and the tumor weight was significantly decreased in LINC-PINT overexpression group compared to the control group. Correspondingly, the positive Ki67 foci was decreased while TUNEL foci was increased in LINC-PINT overexpression group. Mechanically, we verified XRCC6 as a new binding protein of LINC-PINT through RNA binding domains prediction, RIP and colocalization of LINC-PINT and XRCC6. By binding to XRCC6, LINC-PINT interfered the formation of DNA-PK complex, regulated mitochondria accumulation status and affected the modification of apoptosis proteins, leading to more cell apoptosis.<br />Conclusion: Our study provided the first evidence that LINC-PINT promotes cell apoptosis in NPC by binding to XRCC6 and affecting its function.<br />Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier GmbH. All rights reserved.)
- Subjects :
- Humans
Animals
Mice
Gene Expression Regulation, Neoplastic
Cell Proliferation
Mice, Nude
Cell Line, Tumor
Nasopharyngeal Carcinoma pathology
Nasopharyngeal Carcinoma metabolism
Nasopharyngeal Carcinoma genetics
RNA, Long Noncoding genetics
RNA, Long Noncoding metabolism
Nasopharyngeal Neoplasms pathology
Nasopharyngeal Neoplasms metabolism
Nasopharyngeal Neoplasms genetics
Apoptosis
Ku Autoantigen metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1618-0631
- Volume :
- 260
- Database :
- MEDLINE
- Journal :
- Pathology, research and practice
- Publication Type :
- Academic Journal
- Accession number :
- 39032384
- Full Text :
- https://doi.org/10.1016/j.prp.2024.155460