Unlocking the Therapeutic Potential of LncRNA in Hypopharynx Squamous Cell Carcinoma.

Background: Identifying the key molecular targets in hypopharynx squamous cell carcinoma (HSCC) is crucial for understanding this prevalent and highly fatal type of head and neck tumor. The study aims to enhance comprehension of the HSCC process by accurately identifying these key molecular targets.

Materials And Methods: In this study, we examined 47 clinical tissue samples from individuals diagnosed with HSCC using RNA-seq high-throughput assay. Quantitative real-time PCR (RT-PCR) was used to compare long non-coding RNA (lncRNA) bladder cancer-associated transcript 1 () expression in HSCC tissues versus adjacent non-tumor tissues. The influence of highly expressed lncRNA on prognostic survival was assessed. Subsequently, we cultured human pharynx squamous cell carcinoma FaDu cells. After reducing lncRNA expression, we assessed FaDu cell proliferation, invasion, and migration using Cell Counting kit-8 (CCK-8) assay, colony formation assay, EUD assay, Transwell assay, and scratch assay. Additionally, liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS) and western blotting analysis were used to analyze proteins that bind to lncRNA . During experiments, mice received subcutaneous injections of FaDu cells transfected with lncRNA shRNA or Scr plasmid (Control) in the dorsal region to observe and compare tumor growth. Lastly, tumor tissues underwent hematoxylin-eosin (HE) and immunohistochemical (IHC) staining.

Results: lncRNA was screened as one of the most significant genes among the group of differentially expressed lncRNAs. RT-PCR exhibited elevated lncRNA expression in HSCC tissues when compared to non-tumor tissues ( < 0.001). Furthermore, increased lncRNA expression correlated with advanced clinical stages, heightened lymphatic invasion, and a poor prognosis. Subsequent experiments solidified our observations, demonstrating lncRNA 's promotion of HSCC cell proliferation ( < 0.05), migration ( < 0.01), and invasion ( < 0.01) compared with the control group. Moreover, LC-MS/MS identified signal transducer and activator of transcription 3 (STAT3) and Prohibitin 2 (PHB2) as lncRNA -binding proteins and sh-lncRNA inhibits STAT3/AKT phosphorylation ( < 0.01) and alters the subcellular distribution of PHB2 and P21 compared with the control group ( < 0.01). Moreover, experiments showed that lncRNA inhibition suppresses tumorigenicity in an HSCC xenograft model compared to the control group ( < 0.01).

Conclusions: lncRNA is highly expressed in HSCC tumor tissues and plays a crucial role in the development of HSCC and . This increased expression may be caused by STAT3/AKT pathway activation, consequently inhibiting P21 expression through PHB2.