Unlocking the Therapeutic Potential of LncRNA BLACAT1 in Hypopharynx Squamous Cell Carcinoma

doi:10.24976/Discov.Med.202436182.51

科研成果详情

题名	Unlocking the Therapeutic Potential of LncRNA BLACAT1 in Hypopharynx Squamous Cell Carcinoma
作者	Liu, Fan-li1,2,3,4; Zhang, Zhan-cheng 1,5; Zhou, Sheng-li 1,2; Liu, Xu-liang 1,2; Xu, Wei 1,2
发表日期	2024-03
发表期刊	DISCOVERY MEDICINE 影响因子和分区
语种	英语
原始文献类型	Article
关键词	hypopharynx squamous cell carcinoma bioinformatics analysis STAT3/AKT PHB2/P21
其他关键词	CANCER ; PROHIBITIN-2 ; EXPRESSION ; SURVIVAL ; P21
摘要	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 (BLACAT1) expression in HSCC tissues versus adjacent non -tumor tissues. The influence of highly expressed lncRNA BLACAT1 on prognostic survival was assessed. Subsequently, we cultured human pharynx squamous cell carcinoma FaDu cells. After reducing lncRNA BLACAT1 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 BLACAT1. During in vivo experiments, mice received subcutaneous injections of FaDu cells transfected with lncRNA BLACAT1 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 BLACAT1 was screened as one of the most significant genes among the group of differentially expressed lncRNAs. RT-PCR exhibited elevated lncRNA BLACAT1 expression in HSCC tissues when compared to non -tumor tissues (p < 0.001). Furthermore, increased lncRNA BLACAT1 expression correlated with advanced clinical stages, heightened lymphatic invasion, and a poor prognosis. Subsequent in vitro experiments solidified our observations, demonstrating lncRNA BLACAT1's promotion of HSCC cell proliferation (p < 0.05), migration (p < 0.01), and invasion (p < 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 BLACAT1-binding proteins and sh-lncRNA BLACAT1 inhibits STAT3/AKT phosphorylation (p < 0.01) and alters the subcellular distribution of PHB2 and P21 compared with the control group (p < 0.01). Moreover, in vivo experiments showed that lncRNA BLACAT1 inhibition suppresses tumorigenicity in an HSCC xenograft model compared to the control group (p < 0.01). Conclusions: lncRNA BLACAT1 is highly expressed in HSCC tumor tissues and plays a crucial role in the development of HSCC in vitro and in vivo. This increased expression may be caused by STAT3/AKT pathway activation, consequently inhibiting P21 expression through PHB2.
资助项目	National Natural Sci-ence Foundation of China [82172961]; Major Sci-ence and Technology Plan Project of Hainan Province [ZDKJ202005]
出版者	DISCOVERY MEDICINE
ISSN	1539-6509
EISSN	1944-7930
卷号	36 期号:182 页码:546-558
DOI	10.24976/Discov.Med.202436182.51
页数	13
WOS类目	Medicine, Research & Experimental
WOS研究方向	Research & Experimental Medicine
WOS记录号	WOS:001197181200018
收录类别	SCIE
PubMed ID	38531795
通讯作者地址	[Xu, Wei]Shandong Univ, Shandong Prov ENT Hosp, Cheeloo Coll Med, Dept Otorhinolaryngol Head & Neck Surg, Jinan 250012, Shandong, Peoples R China. ; [Xu, Wei]Shandong Prov Key Lab Otol, Jinan 250022, Shandong, Peoples R China.
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/212461
专题	附属第二医院_耳鼻咽喉科第二临床医学院，附属第二医院、育英儿童医院
通讯作者	Xu, Wei
作者单位	1.Shandong Univ, Shandong Prov ENT Hosp, Cheeloo Coll Med, Dept Otorhinolaryngol Head & Neck Surg, Jinan 250012, Shandong, Peoples R China; 2.Shandong Prov Key Lab Otol, Jinan 250022, Shandong, Peoples R China; 3.Wenzhou Med Univ, Affiliated Hosp 2, Dept Otolaryngol Head & Neck Surg, Wenzhou 325027, Zhejiang, Peoples R China; 4.Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou 325027, Zhejiang, Peoples R China; 5.Fourth Hosp Jinan, Dept Otorhinolaryngol, Jinan 250031, Shandong, Peoples R China
第一作者单位	附属第二医院_耳鼻咽喉科; 第二临床医学院，附属第二医院、育英儿童医院
推荐引用方式 GB/T 7714	Liu, Fan-li,Zhang, Zhan-cheng,Zhou, Sheng-li,et al. Unlocking the Therapeutic Potential of LncRNA BLACAT1 in Hypopharynx Squamous Cell Carcinoma[J]. DISCOVERY MEDICINE,2024,36(182):546-558.
APA	Liu, Fan-li, Zhang, Zhan-cheng, Zhou, Sheng-li, Liu, Xu-liang, & Xu, Wei. (2024). Unlocking the Therapeutic Potential of LncRNA BLACAT1 in Hypopharynx Squamous Cell Carcinoma. DISCOVERY MEDICINE, 36(182), 546-558.
MLA	Liu, Fan-li,et al."Unlocking the Therapeutic Potential of LncRNA BLACAT1 in Hypopharynx Squamous Cell Carcinoma".DISCOVERY MEDICINE 36.182(2024):546-558.