ETS Proto-Oncogene 1-activated muskelin 1 antisense RNA drives the malignant progression of hepatocellular carcinoma by targeting miR-22-3p to upregulate ETS Proto-Oncogene 1.

Abstract

Long noncoding RNA muskelin 1 antisense RNA (MKLN1-AS) acted as an oncogenic regulator in hepatocellular carcinoma (HCC). This study was performed to investigate the functional mechanism of MKLN1-AS. MKLN1-AS, microRNA-22-3p (miR-22-3p) and ETS Proto-Oncogene 1 (ETS1) levels were examined using reverse transcription-quantitative polymerase-chain reaction. Protein expression was detected by Western blot. The target relation was analyzed by dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay. Cell proliferation ability was determined through cell counting kit-8 assay, colony formation assay and ethylenediurea assay. Angiogenesis was examined by tube formation assay. Cell migration and invasion were assessed via transwell assay. In vivo research was conducted by xenograft tumor model in nude mice. MKLN1-AS was upregulated in HCC tissues and cells. ETS1 promoted the ETS1 expression by binding to the 582-596 sites. Silence of MKLN1-AS suppressed cell growth, angiogenesis, migration, and invasion. MKLN1-AS interacted with miR-22-3p in HCC cells. The function of MKLN1-AS downregulation was relieved by miR-22-3p inhibition in HCC cells. ETS1 was validated as a target of miR-22-3p, and MKLN1-AS upregulated the ETS1 expression by sponging miR-22-3p. Overexpression of miR-22-3p retarded HCC progression by downregulating the level of ETS1. Tumor growth in vivo was also enhanced by MKLN1-AS through the regulation of miR-22-3p/ETS1 axis. These data demonstrated that ETS1-mediated MKLN1-AS contributed to the malignant phenotypes of HCC cells via depending on the miR-22-3p/ETS1 regulatory axis.

• Authors: Guozheng Pan, Jian Zhang, Faping You, Tao Cui, Peng Luo, Shuling Wang, Xiaomei Li, Qingzhong Yuan
• Journal: Bioengineered (Bioengineered) Vol. 13 Issue 1 Pg. 1346-1358 (01 2022) ISSN: 2165-5987 [Electronic] United States
• PMID: 34983308 (Publication Type: Journal Article)

Chemical References

• ETS1 protein, human
• MIRN22 microRNA, human
• MicroRNAs
• Proto-Oncogene Protein c-ets-1
• RNA, Long Noncoding

Topics

• Animals
• Carcinoma, Hepatocellular (genetics, pathology)
• Case-Control Studies
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Disease Progression
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Liver Neoplasms (genetics, pathology)
• Male
• Mice
• MicroRNAs (genetics)
• Neoplasm Transplantation
• Proto-Oncogene Protein c-ets-1 (genetics)
• RNA, Long Noncoding (genetics)
• Up-Regulation