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Long noncoding RNA MACC1-AS1 is a potential sponge of microRNA-34a in cervical squamous cell carcinoma and upregulates cyclin-dependent kinase 6.

ABSTRACT: The present study aimed to investigate the role of long noncoding RNA MACC1-AS1 in cervical squamous cell carcinoma (CSCC). In the present study MACC1-AS1 expression as analyzed using reverse transcription-quantitative PCR. The interactions between MACC1-AS1 and miR-34a was analyzed via overexpression experiments. Cell cycle and proliferation analyses were performed to analyze the roles of MACC1-AS1 in regulating cancer cell cycle progression and cell proliferation. It was observed that MACC1-AS1 was upregulated in CSCC, and its expression levels were elevated with the increase in clinical stage. Bioinformatics analysis revealed that MACC1-AS1 may be a sponge of miR-34a, which can target cyclin-dependent kinase 6 (CDK6). In CSCC cells, MACC1-AS1 overexpression led to upregulation of CDK6, while miR-34a overexpression had the opposite effect and reduced the effects of MACC1-AS1 overexpression in co-transfected cells. Cell cycle and proliferation analyses demonstrated that MACC1-AS1 and CDK6 promoted cell cycle progression and cell proliferation. By contrast, miR-34a had the opposite effect on cell cycle proliferation and cell proliferation, reducing the effects induced by MACC1-AS1 overexpression. Therefore, the lncRNA MACC1-AS1 may serve as a sponge of miR-34a to upregulate CDK6, thereby promoting cell cycle progression and cell proliferation.

SUBMITTER: Jin J

PROVIDER: S-EPMC7039179 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Long noncoding RNA MACC1-AS1 is a potential sponge of microRNA-34a in cervical squamous cell carcinoma and upregulates cyclin-dependent kinase 6.

Jin Jieqiong J Chen Xuemei X Chen Jing J Geng Xin X

Oncology letters 20200124 3

The present study aimed to investigate the role of long noncoding RNA MACC1-AS1 in cervical squamous cell carcinoma (CSCC). In the present study MACC1-AS1 expression as analyzed using reverse transcription-quantitative PCR. The interactions between MACC1-AS1 and miR-34a was analyzed via overexpression experiments. Cell cycle and proliferation analyses were performed to analyze the roles of MACC1-AS1 in regulating cancer cell cycle progression and cell proliferation. It was observed that MACC1-AS ...[more]

PMID: 32194733

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Project description:Although the functions of long noncoding RNA (lncRNA) called FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) have been well studied in multiple human cancer types, its expression status and detailed roles in cervical cancer remain unknown and merit investigation. This study was aimed at assessing FOXD2-AS1 expression in cervical cancer and at determining its effects on the aggressive behavior of cervical cancer in vitro and in vivo. Expression of FOXD2-AS1 in cervical cancer tissues and cell lines was determined via reverse-transcription quantitative PCR. The effects of FOXD2-AS1 on cervical cancer cells were examined by a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, flow-cytometric analysis, migration and invasion assays, and an in vivo tumorigenicity assay. FOXD2-AS1 was found to be significantly upregulated in cervical cancer tissues and cell lines. High FOXD2-AS1 expression was notably linked with the Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, and depth of cervical invasion in patients with cervical cancer. Kaplan-Meier survival analysis revealed significantly shorter overall survival of patients when the tumor expression of FOXD2-AS1 was higher in comparison with those in patients with lower FOXD2-AS1 expression. In vitro functional assays revealed that downregulation of FOXD2-AS1 led to suppression of proliferation, migration, and invasiveness as well as to the induction of apoptosis of cervical cancer cells. In addition, FOXD2-AS1 silencing hindered tumor growth in vivo. Mechanism investigation revealed that FOXD2-AS1 functioned as a molecular sponge of microRNA-760 (miR-760). Furthermore, hepatoma-derived growth factor (HDGF) was validated as a direct target gene of miR-760 in cervical cancer cells. Moreover, an miR-760 knockdown reversed the effects of FOXD2-AS1 silencing on cervical cancer cells. FOXD2-AS1 possesses significant oncogenic activity in cervical cancer progression; this activity is mediated by sponging of miR-760 with consequent upregulation of HDGF. The FOXD2-AS1-miR-760-HDGF axis might harbor promising targets for novel treatment strategies of cervical cancer.

Project description: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.

Dataset Information

Long noncoding RNA MACC1-AS1 is a potential sponge of microRNA-34a in cervical squamous cell carcinoma and upregulates cyclin-dependent kinase 6.

Publications

Long noncoding RNA MACC1-AS1 is a potential sponge of microRNA-34a in cervical squamous cell carcinoma and upregulates cyclin-dependent kinase 6.

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