LncRNA TMPO‐AS1 promotes hepatocellular carcinoma cell proliferation, migration and invasion through sponging miR‐329‐3p to stimulate FOXK1‐mediated AKT/mTOR signaling pathway

Abstract

Purpose Hepatocellular carcinoma (HCC) is one of the leading causes of cancer‐related death worldwide. Numerous analyses have revealed the abnormal expression of long non‐coding RNAs (lncRNAs) in HCC cells. This study aims to explore biological functions of lncRNA TMPO‐AS1 (TMPO antisense RNA 1) in HCC cell proliferation, apoptosis, invasion and migration. Methods The gene expression in HCC tissues and cell lines were measured by qRT‐PCR. The role of TMPO‐AS1 in HCC was confirmed by CCK‐8, colony formation, TUNEL, transwell and western blot as well as by in vivo experiments. RNA pull down and luciferase reporter assays were utilized to prove the binding relationship between TMPO‐AS1/FOXK1 (forkhead box K1) andmiR‐329‐3p. Rescue assays elucidated the regulatory effects of TMPO‐AS1/miR‐329‐3p/FOXK1/AKT/mTOR pathway on cellular activities in HCC. Results TMPO‐AS1was upregulated in HCC tissues and cells and its depletion inhibits HCC cell proliferation, invasion, migration, and EMT process as well as tumor growth. Furthermore, TMPO‐AS1 could bind with miR‐329‐3p, which suppressed HCC cell proliferation. FOXK1 served as the target gene of miR‐329‐3p and TMPO‐AS1 upregulated FOXK1 by sponging miR‐329‐3p in HCC cells. Additionally, FOXK1 overexpression or miR‐329‐3p inhibitor neutralized the repressing effects of TMPO‐AS1 knockdown on HCC development. Finally, it verified that TMPO‐AS1 could regulate AKT/mTOR pathway via FOXK1 to promote HCC. Conclusion TMPO‐AS1 contributes to HCC progression by sponging miR‐329‐3p to activate FOXK1‐mediated AKT/mTOR signaling pathway.

The Long Non-coding RNA TMPO-AS1  Promotes Bladder Cancer Growth and Progression via OTUB1-induced E2F1 Deubiquitination

“…Here, we found that TMPO-AS1 is highly expressed in BC, and correlates with poor prognoses. We performed in vitro experiment and proved that TMPO-AS1 could function as an oncogene, consistent with previous studies [17,50,51,52].…”

“…Numerous studies have revealed that TMPO-AS1 contributes to tumorigenesis. However, most of them suggest that this is mediated via a TMPO-AS1-miRNA-mRNA axis [17,18,51,52], while others propose that TMPO-AS1 forms RNA-RNA complexes to regulate gene expression [19,55]. Very recently, a study has shown that TMPO-AS1 promotes BC cell growth via a TMPO-AS1/miR-98-5p/EBF1 positive feedback loop [51].…”

“…Moreover, recent studies have demonstrated that upregulated TMPO antisense RNA 1 (TMPO-AS1) serves as competing endogenous RNA to sponge microRNAs (miRNAs) in multiple carcinomas including hepatocellular carcinoma, thyroid cancer, lung adenocarcinoma, and breast cancer [17,18,19,20]. However, whether TMPO-AS1 plays a role by interacting with other molecules in BC is an interesting question requiring further investigation.…”

<p>LncRNA TMPO-AS1 Promotes Proliferation and Invasion by Sponging miR-383-5p in Glioma Cells</p>

“…As one of the important oncogenic lncRNAs in many types of cancers, lncRNA TMPO-AS1 is involved in different biological processes in tumorigenesis, including cell proliferation, apoptosis, invasiveness, and so on. 15 , 16 Qin et al demonstrated that downregulation of TMPO-AS1 inhibited cell proliferation, colony formation, migration and invasion in vitro, and suppressed tumor growth in non-small cell lung cancer in vivo. 6 Zhao et al reported that silence of TMPO-AS1 restrained the aggressiveness and the pro-angiogenic activity of ovarian cancer cells, blocking ovarian cancer development.…”

TMPO-AS1 Regulates the Aggressiveness-Associated Traits of Nasopharyngeal Carcinoma Cells Through Sponging miR-320a

“… 8 In hepatocellular carcinoma, TMPO-AS1 promotes cancer cells’ proliferation, migration, and invasion through sponging miR-329-3p to stimulate the Forkhead Box K1 (FOXK1)-mediated serine/threonine kinase 1-mammalian target of rapamycin (AKT-mTOR) signaling pathway. 9 Several studies suggest that lncRNAs may function as competing endogenous RNAs (ceRNAs) to regulate the biological function or expression of miRNAs. 10 LncRNA TMPO-AS1 serves as a ceRNA to promote osteosarcoma tumorigenesis by regulating the miR-199a-5p-Wnt Family Member 7B (WNT7B) axis.…”