A novel mechanism by which ACTA2-AS1 promotes cervical cancer progression: acting as a ceRNA of miR-143-3p to regulate SMAD3 expression

Abstract

Background: Long non-coding RNAs (LncRNAs) have been increasingly confirmed to be abnormally expressed in human cancer and closely related to tumorigenesis. LncRNA ACTA2-AS1 is abnormally expressed in multiple tumors and participates in their development. However, whether ACTA2-AS1 plays a role in the development of cervical cancer (CC) and the exact mechanism of its role has not been elucidated. Methods: Quantitative real-time PCR (qRT-PCR) was conducted to detect the expression level of messenger RNA of ACTA2-AS1, miR-143-3p and SMAD3 in tumor tissues and cells. Additionally, SMAD3 protein expression by western blots in cells. Small interference RNA against ACTA2-AS1 or SMAD3 and miR-143-3p mimic/inhibitor was designed and transfected into CC cell lines to investigate their correlations and potential impacts on cell function. Cell Counting Kit-8 (CCK-8) assay, colony formation, cell cycle assay, transwell assay and flow cytometry analysis were performed to detect the specific effects on cell line proliferation, metastasis and apoptosis. Results: ACTA2-AS1 was significantly increased in CC tissues and cells and miR-143-3p was down-regulated. Clinically, the higher expression of ACTA2-AS1 was significantly correlated with higher FIGO stage. Loss-of-function assay revealed that silencing of ACTA2-AS1 inhibited cell proliferation, colony formation, migration and promoted apoptosis in CC. Additionally, Pearson correlation analysis showed that the expression of ACTA2-AS1 and miR-143-3p were negatively correlated. Dual-luciferase reporter assay and further mechanistic experiments confirmed that ACTA2-AS1 could sponge and regulate the expression of miR-143-3p. Furthermore, SMAD3 was the target gene of miR-143-3p and ACTA2-AS1 could upregulate SMAD3 through acting as a competitive endogenous RNA (ceRNA) of miR-143-3p. Finally, rescue assay demonstrated that the ACTA2-AS1/miR-143-3p/SMAD3 axis played an important role in the proliferation, migration and apoptosis of CC cells. Conclusions: In summary, our study revealed that ACTA2-AS1 upregulates SMAD3 by competitively binding miR-143-3p, thereby accelerating CC progression. The ACTA2-AS1/miR-143-3p/SMAD3 axis can play a crucial role in cervical carcinogenesis, providing new clues for the early diagnosis and treatment of CC.

RETRACTED ARTICLE: Long non-coding RNA GATA6-AS1 upregulates GATA6 to regulate the biological behaviors of lung adenocarcinoma cells

“…In addition, ectopic expressions of lncRNAs lead to the abnormality of ceRNA regulatory network, in which lncRNAs competitively interact with miRNAs to regulate expression patterns of target genes, thus inducing carcinogenesis and cancer growth [ 18 ]. For example, lncRNA ACTA2-AS1 promotes cervical cancer development through serving as a ceRNA for miR-143-3p to upregulate SMAD3 expression [ 19 ]. Hence, the interaction between GATA6-AS1 and miR-4530 was to be explored in our study.…”

LncRNA MIR503HG promotes hypertrophic scar progression via miR‐143‐3p‐mediated Smad3 expression

“…In addition, it was found that miR-143-3p regulates the expression of Smad3 in cervical cancer. 24 We found the binding site of miR-143-3p on Smad3…”

LncRNA ACTA2-AS1 suppress colon adenocarcinoma progression by sponging miR-4428 upregulation BCL2L11

“…Recently, it was reported that ACTA2-AS1 is significantly over-expressed in cervical cancer, upregulating SMAD3 expression by competitively sponging miR-143-3p [ 15 ]. However, ACTA2-AS1 may act as a tumor suppressor in lung adenocarcinoma and liver cancer cell via sequestering miR-378a-3p and miR-4428 to upregulate the expression of SOX7.…”

“…LncRNA ACTA2-AS1 (ACTA2 Antisense RNA 1) is located at 10q23.31 with five exons [ 12 ]. Recent studies revealed that dysregulation of ACTA2-AS1 has been found to be closely related to poor prognosis of several cancers, such as cervical cancer, hepatocellular carcinoma, liver cancer, breast cancer and lung adenocarcinoma [ 13 – 15 ]. According to previous studies, ACTA2-AS1 may play an important role involved in the development of human cancers.…”