lncRNA NKILA Promotes Warburg Effect and Immune Escape in Intrahepatic Cholangiocarcinoma by Regulating the MTX1/TOMM40 Axis.
[BACKGROUND AND AIMS] Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with high heterogeneity and poor prognosis.
APA
Zhu M, Zhu H, et al. (2025). lncRNA NKILA Promotes Warburg Effect and Immune Escape in Intrahepatic Cholangiocarcinoma by Regulating the MTX1/TOMM40 Axis.. Mediators of inflammation, 2025, 7712817. https://doi.org/10.1155/mi/7712817
MLA
Zhu M, et al.. "lncRNA NKILA Promotes Warburg Effect and Immune Escape in Intrahepatic Cholangiocarcinoma by Regulating the MTX1/TOMM40 Axis.." Mediators of inflammation, vol. 2025, 2025, pp. 7712817.
PMID
41498025
Abstract
[BACKGROUND AND AIMS] Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with high heterogeneity and poor prognosis. Long noncoding RNAs (lncRNAs) play critical roles in tumorigenesis through dysregulated expression. We explored the effects and mechanisms of nuclear transcription factor NF-κB interacting lncRNA (NKILA) in ICC.
[METHODS] Bioinformatic analysis was performed to determine the expression and relationship of NKILA with metaxin 1 (MTX1), and translocase of outer mitochondrial membrane 40 (TOMM40) expression in ICC tissue samples. Cholangiocarcinoma cell lines were cultured in vitro and the transplanted tumor model was constructed in vivo to study the role of NKILA in ICC. Immunohistochemistry (IHC), Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the effects of NKILA on the Warburg effect, autophagy, programed cell death 1 ligand 1 (PD-L1) expression, and CD8 T cytotoxicity in ICC cells. RNA immunoprecipitation (IP) (RIP) assay and RNA-RNA pull down assays were utilized to detect the binding of NKILA and MTX1, and CO-IP was performed to assess the interaction between MTX1 and TOMM40.
[RESULTS] We found that NKILA, MTX1, and TOMM40 were substantially upregulated in ICC tissues, and NKILA silencing reduced MTX1-TOMM40 binding in ICC cells. NKILA facilitated proliferation, invasion, Warburg effects, and autophagy of ICC cells by regulating mammalian target of rapamycin (mTOR) pathway, PD-L1 expression, and CD8 T cytotoxicity, while dichloroacetate (DCA) could reverse these effects. Mechanistically, NKILA binds directly to MTX1 mRNA, which stabilizes MTX1 mRNA and thereby promotes the expression of MTX1 protein. NKILA silencing could inactivate MTX1/TOMM40 axis to inhibit Warburg effect and autophagy-associated immune escape.
[CONCLUSIONS] LncRNA NKILA promotes Warburg effect and immune escape in ICC by regulating the MTX1/TOMM40 axis.
[METHODS] Bioinformatic analysis was performed to determine the expression and relationship of NKILA with metaxin 1 (MTX1), and translocase of outer mitochondrial membrane 40 (TOMM40) expression in ICC tissue samples. Cholangiocarcinoma cell lines were cultured in vitro and the transplanted tumor model was constructed in vivo to study the role of NKILA in ICC. Immunohistochemistry (IHC), Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the effects of NKILA on the Warburg effect, autophagy, programed cell death 1 ligand 1 (PD-L1) expression, and CD8 T cytotoxicity in ICC cells. RNA immunoprecipitation (IP) (RIP) assay and RNA-RNA pull down assays were utilized to detect the binding of NKILA and MTX1, and CO-IP was performed to assess the interaction between MTX1 and TOMM40.
[RESULTS] We found that NKILA, MTX1, and TOMM40 were substantially upregulated in ICC tissues, and NKILA silencing reduced MTX1-TOMM40 binding in ICC cells. NKILA facilitated proliferation, invasion, Warburg effects, and autophagy of ICC cells by regulating mammalian target of rapamycin (mTOR) pathway, PD-L1 expression, and CD8 T cytotoxicity, while dichloroacetate (DCA) could reverse these effects. Mechanistically, NKILA binds directly to MTX1 mRNA, which stabilizes MTX1 mRNA and thereby promotes the expression of MTX1 protein. NKILA silencing could inactivate MTX1/TOMM40 axis to inhibit Warburg effect and autophagy-associated immune escape.
[CONCLUSIONS] LncRNA NKILA promotes Warburg effect and immune escape in ICC by regulating the MTX1/TOMM40 axis.
MeSH Terms
Humans; RNA, Long Noncoding; Cholangiocarcinoma; Cell Line, Tumor; Mice; Animals; Cell Proliferation; Mitochondrial Precursor Protein Import Complex Proteins; Male; Bile Duct Neoplasms; Female; Gene Expression Regulation, Neoplastic; Warburg Effect, Oncologic; Autophagy; Middle Aged; Immunohistochemistry
같은 제1저자의 인용 많은 논문 (5)
- Effects of botulinum toxin type A in patients with painful temporomandibular joint disorders: a systematic review and meta-analysis.
- Designing an Osmium(II) Complex to Inhibit the Growth and Recurrence of Tumors by Integrating Photodynamic Therapy, Chemotherapy, and Immunotherapy.
- A controllable self-amplifying oxidative stress strategy for boosting noninvasive sonodynamic therapy and synergistic immunotherapy.
- The circTIMP2/miR-106a/TIMP2 tumor-suppressive axis versus tumor-derived exosomal counteraction in gastric cancer.
- Regorafenib enhances anti-PDCD1/PD-1 therapeutic efficacy in colorectal cancer by promoting SQSTM1/p62-mediated CD274/PD-L1 degradation.