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Long noncoding RNA PSMA3?AS1 functions as a microRNA?409?3p sponge to promote the progression of non?small cell lung carcinoma by targeting spindlin 1.

ABSTRACT: PSMA3 antisense RNA 1 (PSMA3?AS1), a long noncoding RNA, promotes the progression of esophageal squamous cell carcinoma. However, no study to date has explored the expression or roles of PSMA3?AS1 in non?small cell lung carcinoma (NSCLC). The present study examined the expression profile and role of PSMA3?AS1 in NSCLC. It also aimed to identify how PSMA3?AS1 promotes the malignant phenotype of NSCLC cells. PSMA3?AS1 expression in NSCLC tissues and cell lines was measured by reverse transcription?quantitative polymerase chain reaction. Cell Counting Kit?8, cell apoptosis, Transwell migration and invasion, and xenograft tumor assays were conducted to study the effects of PSMA3?AS1 on the aggressive phenotype of NSCLC cells. Furthermore, bioinformatics analysis, RNA immunoprecipitation, luciferase reporter assay, western blotting, and rescue experiments were used to elucidate the interaction among PSMA3?AS1, microRNA?409?3p (miR?409?3p), and spindlin 1 (SPIN1) in NSCLC cells. In the present study, high levels of PSMA3?AS1 were confirmed in both NSCLC tissues and cell lines. An increased PSMA3?AS1 level was correlated with advanced tumor?node?metastasis stage and increased lymph node metastasis. Patients with NSCLC with high PSMA3?AS1 levels had shorter overall survival than those with low PSMA3?AS1 levels. PSMA3?AS1 depletion significantly decreased NSCLC cell proliferation, migration, and invasion, as well as substantially increased cell apoptosis in vitro. Furthermore, PSMA3?AS1 deficiency decreased NSCLC tumor growth in vivo. Through molecular mechanism assays, it was revealed that PSMA3?AS1 acted as a molecular sponge for miR?409?3p and consequently increased SPIN1 expression. Notably, rescue experiments revealed that the inhibition of miR?409?3p or restoration of SPIN1 expression abrogated the effects of PSMA3?AS1 knockdown in NSCLC cells. Collectively, PSMA3?AS1 functioned as an oncogenic long noncoding RNA in NSCLC. PSMA3?AS1 sponged miR?409?3p and thus increased SPIN1 expression, promoting the aggressive phenotype of NSCLC cells.

SUBMITTER: Wang L

PROVIDER: S-EPMC7448465 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Long noncoding RNA PSMA3‑AS1 functions as a microRNA‑409‑3p sponge to promote the progression of non‑small cell lung carcinoma by targeting spindlin 1.

Wang Lingling L Wu Lei L Pang Jinfeng J

Oncology reports 20200715 4

PSMA3 antisense RNA 1 (PSMA3‑AS1), a long noncoding RNA, promotes the progression of esophageal squamous cell carcinoma. However, no study to date has explored the expression or roles of PSMA3‑AS1 in non‑small cell lung carcinoma (NSCLC). The present study examined the expression profile and role of PSMA3‑AS1 in NSCLC. It also aimed to identify how PSMA3‑AS1 promotes the malignant phenotype of NSCLC cells. PSMA3‑AS1 expression in NSCLC tissues and cell lines was measured by reverse transcription ...[more]

PMID: 32945481

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Project description:BackgroundGastric cancer (GC) is one of the most common malignant tumors worldwide. Currently, the overall survival rate of GC is still unsatisfactory despite progress in diagnosis and treatment. Therefore, studying the molecular mechanisms involved in GC is vital for diagnosis and treatment. CircRNAs, a type of noncoding RNA, have been proven to act as miRNA sponges that can widely regulate various cancers. By this mechanism, circRNA can regulate tumors at the genetic level by releasing miRNA from inhibiting its target genes. The WNT2/β-Catenin regulatory pathway is one of the canonical signaling pathways in tumors. It can not only promote the development of tumors but also provide energy for tumor growth through cell metabolism (such as glutamine metabolism).MethodsThrough RNA sequencing, we found that hsa_circ_0008259 (circLMO7) was highly expressed in GC tissues. After verifying the circular characteristics of circLMO7, we determined the downstream miRNA (miR-30a-3p) of circLMO7 by RNA pull-down and luciferase reporter assays. We verified the effect of circLMO7 and miR-30a-3p on GC cells through a series of functional experiments, including colony formation, 5-ethynyl-2'-deoxyuridine and Transwell assays. Through Western blot and immunofluorescence analyses, we found that WNT2 was the downstream target gene of miR-30a-3p and further confirmed that the circLMO7-miR-30a-3p-WNT2 axis could promote the development of GC. In addition, measurement of related metabolites confirmed that this axis could also provide energy for the growth of GC cells through glutamine metabolism. We found that circLMO7 could promote the growth and metastasis of GC in vivo by the establishment of nude mouse models. Finally, we also demonstrated that HNRNPL could bind to the flanking introns of the circLMO7 exons to promote circLMO7 cyclization.ResultsCircLMO7 acted as a miR-30a-3p sponge affecting the WNT2/β-Catenin pathway to promote the proliferation, migration and invasion of GC cells. Moreover, animal results also showed that circLMO7 could promote GC growth and metastasis in vivo. CircLMO7 could also affect the glutamine metabolism of GC cells through the WNT2/β-Catenin pathway to promote its malignant biological function. In addition, we proved that HNRNPL could promote the self-cyclization of circLMO7.ConclusionsCircLMO7 promotes the development of GC by releasing the inhibitory effect of miR-30a-3p on its target gene WNT2.

Dataset Information

Long noncoding RNA PSMA3?AS1 functions as a microRNA?409?3p sponge to promote the progression of non?small cell lung carcinoma by targeting spindlin 1.

Publications

Long noncoding RNA PSMA3‑AS1 functions as a microRNA‑409‑3p sponge to promote the progression of non‑small cell lung carcinoma by targeting spindlin 1.

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