The roles and molecular mechanisms of long non-coding RNA WT1-AS in the maintenance and development of gastric cancer stem cells

被引：2

作者：

Zhang, Xiaobei ^{[1
]}

Jin, Meng ^{[1
]}

Liu, Shiqi ^{[1
]}

Zang, Mingde ^{[2
]}

Hu, Lei ^{[3
]}

Du, Tao ^{[4
]}

Zhang, Baogui ^{[1
]}

机构：

[1] Jining Med Univ, Affiliated Hosp, Jining 272000, Peoples R China

[2] Fudan Univ, Shanghai Med Coll, Shanghai Canc Ctr, Dept Gastr Canc Surg,Dept Oncol, Shanghai 200032, Peoples R China

[3] Anhui Med Univ, Affiliated Prov Hosp, Dept Gen Surg, Hefei 230001, Peoples R China

[4] Tongji Univ, Shanghai East Hosp, Sch Med, Dept Gastrointestinal Surg, Shanghai 200120, Peoples R China

来源：

HELIYON | 2023年 / 9卷 / 04期

基金：

中国国家自然科学基金;

关键词：

Gastric cancer stem cells; Growth; Metastasis; WT1-AS; RNA sequencing; WILMS-TUMOR; 1; LUNG-CANCER; ALPHA-2-DELTA-1; SUBUNIT; MONOAMINE-OXIDASE; EXPRESSION; PROLIFERATION; CHEMOTHERAPY; HOMEOSTASIS; P53;

D O I：

10.1016/j.heliyon.2023.e14655

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

It has been proposed that cancer stem cells (CSCs) are responsible for almost all malignant phenotypes of tumors. Long non-coding RNA WT1 antisense RNA (WT1-AS) has been found to be implicated in lung cancer cell stemness. However, the roles and molecular mechanisms of WT1AS in the development of gastric cancer stem cells (GCSCs) remain unknown. Our present study showed that WT1-AS negatively regulated WT1 expression in GCSCs. WT1-AS knockdown or Wilms' tumor 1 (WT1) overexpression improved GCSC proliferative and migratory capacities, inhibited GCSC apoptosis, potentiated the resistance of GCSCs to 5-FU, promoted GCSC EMT, induced HUVEC angiogenesis, enhanced GCSC stemness, and facilitated in-vitro 3D GCSC aggregate formation. WT1-AS overexpression exerted reverse effects. WT1-AS ameliorated the malignant phenotypes of GCSCs by down-regulating WT1 in vitro. WT1-AS inhibited tumor growth and metastasis, and reduced tumor stemness in GCSCs-derived (s.c., i.p., and i.v.) xenografts in vivo. Moreover, XBP1 was identified as an upstream regulator of WT1-AS in GCSCs. Also, 4 potential WT1-AS downstream targets (i.e. PSPH, GSTO2, FYN, and PHGDH) in GCSCs were identified. Additionally, CACNA2D1 was demonstrated to be a downstream target of the WT1-AS/ WT axis. XBP1 or CACNA2D1 knockdown exerted an adverse effect on the maintenance of stem cell-like behaviors and characteristics of GCSCs. In conclusion, WT1-AS weakened the stem celllike behaviors and characteristics of GCSCs in vitro and in vivo by down-regulating WT1. Investigations into the molecular mechanisms underlying the complex phenotypes of GCSCs might contribute to the better management of gastric cancer.

引用

页数：18