LncRNA TPT1‐AS1 promotes tumorigenesis and metastasis in epithelial ovarian cancer by inducing TPT1 expression

Abstract

Increasing numbers of studies have confirmed that long noncoding RNA (lnc RNA ) play a critical role in epithelial ovarian cancer ( EOC ) progression. However, the potential function of the lnc RNA tumor protein translationally controlled 1 ( TPT 1) antisense RNA 1 ( TPT 1‐ AS 1) in EOC is unclear. In this study, we aimed to uncover the biological roles and regulatory mechanisms of TPT 1‐ AS 1 in EOC progression and metastasis. First, TPT 1‐ AS 1 expression was significantly higher in EOC metastatic tissue and cell lines than in their respective control counterparts. In addition, ectopic TPT 1‐ AS 1 expression was strongly associated with unfavorable EOC clinicopathological features, including FIGO stage, tumor size and tumor differentiation. TPT 1‐ AS 1 overexpression remarkably induced cell proliferation, migration and invasion, and significantly attenuated cell adhesion ability in vitro and facilitated nude mouse subcutaneous xenograft growth and intraperitoneal metastasis in vivo, while the downregulation of TPT 1‐ AS 1 expression produced the opposite effect in vitro. Mechanistically, TPT 1‐ AS 1 was proven to be primarily distributed in EOC cell nuclei and positively modulated TPT 1 promoter activity and transcription. Moreover, the oncogenic effects of TPT 1‐ AS 1 could be reversed by TPT 1 depletion, and the PI 3K/ AKT signaling pathway downstream of TPT 1 was also altered. These results suggested that TPT 1‐ AS 1 induced EOC tumor growth and metastasis through TPT 1 and downstream PI 3K/ AKT signaling and that TPT 1‐ AS 1 may be a promising therapeutic target for EOC .

Knockdown of TPT1-AS1 inhibits cell proliferation, cell cycle G1/S transition, and epithelial–mesenchymal transition in gastric cancer

“…These findings indicated that TPT1-AS1 may participate as an oncogene in the pathogenesis of GC. Consistently, TPT1-AS1 was remarkably elevated in cervical cancer [18] and ovarian cancer tissues [19]. Moreover, elevated TPT1-AS1 expression predicted worse prognosis in ovarian cancer patients [19].…”

“…Consistently, TPT1-AS1 was remarkably elevated in cervical cancer [18] and ovarian cancer tissues [19]. Moreover, elevated TPT1-AS1 expression predicted worse prognosis in ovarian cancer patients [19]. On the contrary, TPT1-AS1 was found to be decreased and identified as a protective lncRNA in glioblastoma [22].…”

“…Another study also demonstrated that TP73-AS1 accelerates cell growth and metastasis in GC [26]. Interestingly, TPT1-AS1 was proved to promote ovarian cancer tumor growth and metastasis through the downstream PI3K/AKT signaling pathway [19].…”

“…Emerging studies show that antisense lncRNAs (lncRNAs-AS) can modulate cancer progression by functioning as positive or negative regulators of coding genes [14][15][16][17]. Tumor protein translationally controlled 1 antisense RNA 1 (TPT1-AS1) has been studied by Jiang et al who showed that TPT1-AS1 as an oncogenic lncRNA promotes cell growth and metastasis in cervical cancer [18], as well as by Wu et al who further revealed that ectopic TPT1-AS1 expression is strongly associated with unfavorable epithelial ovarian cancer (EOC) clinicopathological features and induces EOC tumor growth and metastasis [19]. Nevertheless, the clinicopathological feature and biological function of TPT1-AS1 in GC remain largely unknown.…”

Overexpression of TPT1-AS1 and SAMMSON and down expression of LINC00961 associated with Advanced Grades of Gastric Cancer

“…Recently, studies have been done to increase the expression of TPT1-AS1 gene, for example, in 2017, Jiang et al studied cervical cancer both in vivo and in vitro, and observed that lncRNA TPT1-AS1 could be involved as an oncogenic agent in the development of cervical cancer, and also, they introduced it as an effective therapeutic goal [9]. In addition, in 2019, Wu et al studied epithelial ovarian cancer, and observed that lncRNA TPT1-AS1 could lead to tumorigenesis and metastasis in epithelial ovarian cancer [24].…”