Knockdown of ACTA2‑AS1 promotes liver cancer cell proliferation, migration and invasion

et al. 2020

Cancer Cell Int

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.

Section: Introductionmentioning

confidence: 99%

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

Luo

et al. 2020

Cancer Cell Int

“…According to bioinformatics analysis, lncRNA actin alpha 2, smooth muscle antisense RNA 1 (ACTA2-AS1) is lowly expressed in tissue samples of stomach adenocarcinoma (STAD). In previous studies, ACTA2-AS1 acts as an oncogene in cervical cancer and ovarian cancer, while serving as antioncogene in liver cancer and lung adenocarcinoma [ 15 , 16 , 17 , 18 ]. However, the functions and mechanism of ACTA2-AS1 in GC have not been reported.…”

Section: Introductionmentioning

confidence: 99%

lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells

Liu

et al. 2022

Open Medicine

Gastric cancer (GC) is one of the most common malignancies in digestive system. Accumulating evidence reveals the critical role of long noncoding RNAs (lncRNAs) in GC development. The study aimed to explore the functions and mechanism of lncRNA actin alpha 2, smooth muscle antisense RNA 1 (ACTA2-AS1) in GC. Reverse transcription-quantitative polymerase chain reaction analyses and subcellular fractionation assays showed that ACTA2-AS1 was lowly expressed in GC cells and was mainly distributed in the cytoplasm. Overexpressed ACTA2-AS1 inhibited GC cell viability, proliferation, migration, invasion, and epithelial-mesenchymal transition process, as suggested by cell counting kit-8 assays, colony formation assays, wound healing assays, Transwell assays and Western blot analyses. Mechanistically, ACTA2-AS1 served as a competing endogenous RNA (ceRNA) to bind with miR-378a-3p and thereby, antagonized the inhibitory effect of miR-378a-3p on the expression of messenger RNA phosphatidylinositol specific phospholipase C X domain containing 2 (PLCXD2). The binding capacity between miR-378a-3p and ACTA2-AS1 (or PLCXD2) was detected by RNA pulldown assays, luciferase reporter assays and RNA immunoprecipitation assays. Moreover, PLCXD2 knockdown rescued the inhibitory effect of ACTA2-AS1 overexpression on malignant behaviors of GC cells. Overall, ACTA2-AS1 inhibits malignant phenotypes of GC cells by acting as a ceRNA to target miR-378a-3p/PLCXD2 axis.

“…LINC00261 plays an antitumor role in LUAD through inducing DNA damage response (Shahabi et al, 2019). ACTA2‐AS1 is a newfound lncRNA that can act as a tumor suppressor in liver cancer 2019; nevertheless, its influences on LUAD progression remain to be investigated. Our current study first unveiled the role of ACTA2‐AS1 in modulating LUAD cell functions.…”

Section: Discussionmentioning

confidence: 99%

“…The abnormal expression of lncRNAs can affect the tumorigenesis or development of malignant tumors, such as lung cancer (Ye, Liu, & Zheng, 2017), hepatocellular carcinoma (Ding, Yang, & Yang, 2018), and squamous cell carcinoma of the head and neck (Di Agostino et al, 2018). Actin alpha 2, smooth muscle antisense RNA 1 (ACTA2‐AS1) is a lncRNA that has been revealed to be a tumor suppressor in liver cancer (Zhou & Lv, 2019); nevertheless, its influences on LUAD progression remain to be investigated. In our current study, we focused on the role of ACTA2‐AS1 in modulating LUAD cell functions.…”

Section: Introductionmentioning

confidence: 99%

ACTA2‐AS1 suppresses lung adenocarcinoma progression via sequestering miR‐378a‐3p and miR‐4428 to elevate SOX7 expression

Ying

Cell Biology International

Long

et al. 2020

Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer. The abnormal expression of long noncoding RNAs (lncRNAs) can facilitate or suppress the development of malignant tumors. lncRNA actin alpha 2, smooth muscle antisense RNA 1 (ACTA2‐AS1) has been reported to function as a tumor suppressor in liver cancer, nevertheless, its influences on LUAD remain to be investigated. In this paper, ACTA2‐AS1 was identified as a downregulated lncRNA in LUAD samples and cells. Functionally, ACTA2‐AS1 overexpression restrained cell proliferation but accelerated cell apoptosis in LUAD. In addition, we determined the suppressive effect of ACTA2‐AS1 on LUAD cell invasion, migration, and epithelial–mesenchymal transition progress. Mechanistically, ACTA2‐AS1 exert functions as a competing endogenous RNA through serving as a sponge for microRNA‐378a‐3p (miR‐378a‐3p) and microRNA‐4428 (miR‐4428) to elevate SRY‐related high‐mobility group box 7 (SOX7) expression. Importantly, SOX7 silencing could recover the ACTA2‐AS1‐mediated cell functions. To summarize, ACTA2‐AS1 suppresses the malignant processes of LUAD cells through sequestering miR‐378a‐3p and miR‐4428 to augment SOX7 expression.