<p>High ACTN1 Is Associated with Poor Prognosis, and ACTN1 Silencing Suppresses Cell Proliferation and Metastasis in Oral Squamous Cell Carcinoma</p>

Abstract

Oral squamous cell carcinoma (OSCC) is a common malignancy of the oral cavity. As the survival rate of OSCC patients is low, it is crucial to explore new markers and therapeutic targets for early diagnosis of the disease. A high level of actinin alpha 1 (ACTN1) in patients could serve as an independent prognostic factor of acute myeloid leukemia. However, the role of ACTN1 in OSCC remains unclear. In the present study, we aimed to investigate the role of ACTN1 in OSCC. Methods: ACTN1 protein levels in tissues were determined by immunohistochemical (IHC) staining. The correlation of ACTN1 expression with clinicopathological features and prognosis was analyzed. Univariate and multivariate analyses were performed. The effect of ACTN1 knockdown on cell proliferation, migration, invasion, apoptosis, epithelial-mesenchymal transition (EMT), and the cell cycle was evaluated using Western blotting, Cell Counting Kit-8 (CCK8) assays, flow cytometry analysis, transwell assays, wound-healing assays, and nude mouse models of subcutaneous xenograft and pulmonary metastasis. Results: Based on the total score of ACTN1 IHC staining analysis, ACTN1 expression was found to be low in 10 normal mucosal tissues, 48 normal mucosal tissues adjacent to OSCC, and 19 OSCC tissues, but high in 29 OSCC tissues. ACTN1 protein levels were significantly associated with the clinical stage and node metastasis, and a high ACTN1 protein level indicated poor prognosis. Moreover, ACTN1 expression was an independent predictor of poor prognosis of OSCC. Using in vitro assays, we found that ACTN1 knockdown could induce cell cycle arrest, promote apoptosis, and inhibit EMT and cell proliferation, migration, and invasion in the OSCC cell lines, SCC-15 and HSC-3. Moreover, ACTN1 knockdown inhibited subcutaneous tumor growth and pulmonary metastasis in vivo. Conclusion: ACTN1 levels were significantly associated with the clinical stage and node metastasis, and a high ACTN1 protein level indicated poor prognosis. Moreover, ACTN1 knockdown could suppress cell proliferation and metastasis of OSCC. Our results suggested that ACTN1 may serve as a diagnostic and prognostic marker of OSCC.

ACTN1 supports tumor growth by inhibiting Hippo signaling in hepatocellular carcinoma

“…ACTN1 has been proved to be associated with the poor prognosis in breast cancer, oral squamous cell carcinoma, and acute lymphoblastic leukemia [26][27][28]. Targeting ACTN1 by Oroxylin A could remodel stromal microenvironment and restrain breast cancer metastasis [29].…”

Adaptor Protein Complex 1 Sigma 3 Is Highly Expressed in Glioma and Could Enhance Its Progression

“…The researchers found that CALU could be used as a potential serum biomarker for glioblastoma through a significant analysis of the microarray. ACTN1, a gene related to the microenvironment, shows prognostic value in patients with malignant glioma [22].…”

α-Actinin1 promotes tumorigenesis and epithelial-mesenchymal transition of gastric cancer via the AKT/GSK3β/β-Catenin pathway

“…ACTN1 has been reported to show up-regulation within BC, which participates in cancer progression by inducing partial EMT [16]. Similarly, the aberrant expression of ACTN1 has been observed in oral, colon, hepatocellular carcinoma, acute myeloid leukemia, and lung adenocarcinoma, contributing to tumor oncogenesis and metastasis by diverse signaling pathways such as Hippo signaling and FAK/Src/ JAK2/STAT3 signaling [16][17][18][19][20][21][22][23]. These results indicate that ACTN1 may participate in tumor occurrence and development.…”