MicroRNA‑652 promotes cell proliferation and osteosarcoma invasion by directly targeting KLF9

Abstract

Previous studies have demonstrated that various microRNAs (miRNAs or miRs) are abnormally expressed in osteosarcoma (OS) and serve roles in its malignant development. An in-depth understanding of the specific roles of dysregulated miRNAs in OS may be important for cancer research and the identification of novel therapeutic targets. In the current study, reverse transcription-quantitative PCR was performed to determine miR-652 expression in OS tissues and cell lines. Cell Counting Kit-8 and Transwell invasion assays were used for assessing the effect of miR-652 on the proliferation and invasion of OS cells. Herein, miR-652 expression was assessed in OS and the effects and molecular mechanisms of miR-652 in OS cells were examined. The results revealed that miR-652 expression was significantly upregulated in OS tissues and cell lines compared with adjacent normal tissues and a normal human osteoblast cell line. Furthermore, miR-652 downregulation inhibited the proliferation and invasion of OS cells. miR-652 was also demonstrated to directly interact with the 3'-untranslated region of kruppel-like factor 9 (KLF9) and miR-652 negatively regulated KLF9 expression in OS cells. miR-652 and KLF9 mRNA levels were also revealed to be inversely correlated in OS tissues. Treatment with KLF9 small interfering RNA abolished the suppression of OS proliferation and invasion induced by miR-652 downregulation. miR-652 may serve an oncogenic role in OS cells by targeting KLF9 directly. The results also indicated that miR-652 may be an effective novel therapeutic target for the treatment of patients with OS.

Krüppel-like Factor 9 (KLF9) Suppresses Hepatocellular Carcinoma (HCC)-Promoting Oxidative Stress and Inflammation in Mice Fed High-Fat Diet

“…KLF9 is an evolutionarily well-conserved transcriptional regulator implicated as a tumor/metastasis suppressor in liver [ 24 , 25 ], endometrium [ 36 , 37 ], colon and rectum [ 38 ], breast [ 39 ], glioblastoma [ 40 ], ovary [ 41 ], and osteosarcoma [ 42 ]. Nevertheless, the underlying mechanism of its tumor-suppressive action for any given tissue remains undefined.…”

Circular RNA_0078767 upregulates Kruppel-like factor 9 expression by targeting microRNA-889, thereby inhibiting the progression of osteosarcoma

“…KLF9 is considered to be a tumor-suppressive gene, and KLF9 is downregulated in non-small cell lung cancer, breast cancer, colorectal cancer and other cancers, and KLF9 partakes in inhibiting the malignant phenotypes of cancer cells [ 52–54 ]. Moreover, KLF9 is reportedly under-expressed in OS cells and tissues and it participates in modulating the malignant progression of OS [ 55 , 56 ]. Reportedly, miR-889 targets KLF9 in non-small cell lung cancer and breast cancer cells [ 17 , 18 ].…”

Upregulation of microRNA miR-652-3p is a prognostic risk factor for hepatocellular carcinoma and regulates cell proliferation, migration, and invasion

“…In human and rat atherosclerotic plaques, miR-652-3p is up-regulated and participates in its progression [ 31 ]. Osteosarcoma tissue and cell line miR-652-3p are significantly elevated and are involved in cell proliferation and migration [ 32 ]. miR-652-3p was remarkedly elevated in tumor tissue of patients with uveal melanoma [ 33 ].…”

“…miRNA plays its specific function by regulating its target genes, so we try to explore them. Previous studies have found that Kuppel-like factor 9 (KLF9) is a potential target gene of miR-652 and participated in the regulation of proliferation and invasion of osteosarcoma by miR-652 [ 32 ]. And the role of KLF9 in HCC has been revealed to some extent in previous studies.…”