Targeting long non-coding RNA H19 attenuates PKM2 deficiency-driven stemness property in tongue cancer.

Authors

Wan-Hsuan Sun, Ta-Jung Peng, Ru-Min Hsieh, Jyun-Wei Yang, Yu-Wen Tang, Kuang-Hui Sun

Published in

Biomedical journal. Pages 101016. Jul 12, 2026. Epub Jul 12, 2026.

Abstract

Cancer stem cells (CSCs) drive tumor recurrence and metastasis via metabolic reprogramming. Although pyruvate kinase M2 (PKM2) is associated with poor prognosis in head and neck cancer (HNC), the loss of PKM2 promotes tumor formation in mice. Long non-coding RNAs (lncRNAs) have been widely implicated in cancer stemness regulation. However, their roles in PKM2 deficiency-mediated tumor progression remain unclear.
PKM2 was knocked out in SAS tongue cancer cells using the CRISPR/Cas9 system. Stemness markers, sphere formation, and drug resistance were examined in CSCs. Whole-transcriptome analysis profiled metabolic, signaling, and lncRNA networks in PKM2-deficient CSCs. Reporter assay and signaling inhibitors were used to validate the pathways for PKM2 knockout-induced H19 expression in CSCs. Lentivirus-mediated shRNA silencing was used to knock down lncRNA H19 for functional analyses.
PKM2 knockout inhibited parental SAS cell clonogenicity and motility, but promoted sphere formation, stemness-related gene expression, invasiveness, and chemoresistance in CSCs. Transcriptomic and RT-qPCR analyses revealed lncRNA H19 gene upregulation in PKM2-deficient CSCs. Mechanistically, reporter assays confirmed c-Myc signaling activation, and Hedgehog or c-Myc signaling blockade inhibited this PKM2 deficiency-induced H19 expression. Functionally, H19 silencing further impaired clonogenicity and motility in PKM2-deficient parental cells, and effectively suppressed the sphere formation, stemness-related gene expression, invasive capacity, and chemoresistance of CSCs promoted by PKM2 deficiency.
PKM2 loss promotes tongue cancer stemness via the induction of lncRNA H19. Co-targeting the PKM2/H19 axis may be a promising therapeutic strategy for tongue cancer.

PMID:
42437633
Bibliographic data and abstract were imported from PubMed on 13 Jul 2026.

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