LncRNA DANCR promotes the proliferation, migration, and invasion of tongue squamous cell carcinoma cells through miR-135a-5p/KLF8 axis

Abstract

Background: Tongue squamous cell carcinoma (TSCC) is a most invasive cancer with high mortality and poor prognosis. It is reported that lncRNA DANCR has implications in multiple types of cancers. However, its biological role and underlying mechanism in TSCC progress are not well elucidated. Methods: Our present study first investigated the function of DANCR on the proliferation, migration and invasion of TSCC cells by silencing or overexpressing DANCR. Further, the miR-135a-5p-Kruppel-like Factor 8 (KLF8) axis was focused on to explore the regulatory mechanism of DANCR on TSCC cell malignant phenotypes. Xenografted tumor growth using nude mice was performed to examine the role of DANCR in vivo. Results: DANCR knockdown reduced the viability and inhibited the migration and invasion of TSCC cells in vitro, while ectopic expression of DANCR induced opposite effects. In vivo, the tumor growth and the expression of matrix metalloproteinase (MMP)-2/9 and KLF8 were also blocked by DANCR inhibition. In addition, we found that miR-135-5p directly targeted DANCR, which was negatively correlated with DANCR on TSCC progression. Its inhibition reversed the beneficial effects of DANCR silence on TSCC malignancies. Furthermore, the expression of KLF8 evidently altered by both DANCR and miR-135a-5p. Silencing KLF8 using its specific siRNA showed that KLF8 was responsible for the induction of miR-135a-5p inhibitor on TSCC cell malignancies and MMP-2/9 expression. Conclusions: These findings, for the first time, suggest that DANCR plays an oncogenic role in TSCC progression via targeting miR-135a-5p/KLF8 axis, which provides a promising biomarker and treatment approach for preventing TSCC.

MiR-135a biogenesis and regulation in malignancy: a new hope for cancer research and therapy

“…MiR-135a is also sponged by SNHG16, and this process is promoted by activation of the JAK2/STAT3 pathway 51 . The inhibition of miR-135a by DANCR was also reported in pancreatic cancer and tongue squamous cell carcinoma cells, which resulted in promoted cancer cell proliferation and invasion 49 , 53 . MiR-135a was also predicted to interact with lncRNA KIAA0125 and may participate in the development of ameloblastoma 54 , 55 .…”

Drug Response Associated With and Prognostic lncRNAs Mediated by DNA Methylation and Transcription Factors in Colon Cancer

“…Noticeably, lncRNA SENCR could interact with 356 mRNA in colon cancer. Previous studies had reported the role of SENCR in multiple human cancers ( Jiang et al, 2017 ; Xu et al, 2019 ; Zheng et al, 2019 ). DANCR had also been proven to promote the proliferation and metastasis of colorectal cancer via miR-577 sponging ( Wang et al, 2018a ).…”

miR-135a Reduces Osteosarcoma Pulmonary Metastasis by Targeting Both BMI1 and KLF4

“…miRNAs are characterized as a group of endogenous noncoding RNAs that play key roles by binding to the proteincoding genes of mRNAs to direct their posttranscriptional repression and to regulate approximately 30%-50% of human gene expression (33). Previous studies indicated that miR-135 inhibits proliferation, invasion, and metastasis in several cancers, such as lung cancer, breast cancer, prostate cancer, tongue squamous cell carcinoma, and metastatic bone disease (34)(35)(36)(37)(38). Our current data on downregulation of miR-135a in OS are consistent with previous studies (39,40).…”