MicroRNA-1269 is downregulated in glioblastoma and its maturation is regulated by long non-coding RNA SLC16A1 Antisense RNA 1

Abstract

MicroRNA-1269 (miR-1296) promotes esophageal cancer. However, its role in other cancers, such as glioblastoma (GBM) is unclear. We predicted that miR-1269 might interact with long non-coding RNA (lncRNA) SLC16A1 Antisense RNA 1 (SLC16A1-AS1), a critical player in GBM. We then studied the interaction between SLC16A1-AS1 and miR-1269 in GBM. In this study, paired GBM and non-tumor tissues were used to analyze the expression of SLC16A1-AS1 and premature and mature miR-1269. The interaction of SLC16A1-AS1 with premature miR-1269 was analyzed with RNA pull-down assay and dual-luciferase reporter assay. Cellular fractionation assay was applied to determine the subcellular location of SLC16A1-AS1. Overexpression assays were applied to determine the role of SLC16A1-AS1 in miR-1269 maturation. BrdU, Transwell and cell apoptosis assays were performed to analyze the role of SLC16A1-AS1 and miR-1269 in GBM cell proliferation, migration, and invasion. Interestingly, we observed the upregulation of premature miR-1269 and downregulation of mature miR-1269 in GBM. SLC16A1-AS1 was also overexpressed in GBM. The direct interaction of SLC16A1-AS1 with premature miR-1269 was observed. SLC16A1-AS1 suppressed miR-1269 maturation and promoted cell proliferation, migration, and invasion, and inhibited cell apoptosis, while miR-1269 displayed the opposite trend. SLC16A1-AS1 partly reversed the effects of miR-1269 on GBM cell proliferation, movement and apoptosis. Moreover, SLC16A1-AS1 overexpression increased the level of ki-67, CDK4 and Bcl-2 in LN-229 and LN-18 cells. However, miR-1269 could partly reverse the effect of SLC16A-AS1 on protein levels. Overall, miR-1269 is downregulated in GBM and its maturation is regulated by SLC16A1-AS1.

Biological roles of SLC16A1-AS1 lncRNA and its clinical impacts in tumors

“…SLC16A1 antisense RNA 1 (SLC16A1-AS1) is a novel antisense lncRNA which has become a rising star in oncological research. SLC16A1-AS1 exhibits aberrant expression in a variety of cancers, including glioblastoma (GBM) [ 93 , 94 ], oral squamous cell carcinoma (OSCC) [ 95 , 96 ], hepatocellular carcinoma (HCC) [ 97 – 100 ], renal cell carcinoma (RCC) [ 101 ], bladder cancer [ 102 ], cervical squamous cell carcinoma(CSCC) [ 103 ], breast cancer [ 104 – 106 ], osteosarcoma [ 107 ], and non-small cell lung cancer (NSCLC) [ 108 ]. Furthermore, SLC16A1-AS1 exhibits multiple biological roles in these primary malignancies, highlighting its complexity in tumorigenesis and its potential as a tumor biomarker [ 93 – 108 ].…”

“…SLC16A1-AS1 exhibits aberrant expression in a variety of cancers, including glioblastoma (GBM) [ 93 , 94 ], oral squamous cell carcinoma (OSCC) [ 95 , 96 ], hepatocellular carcinoma (HCC) [ 97 – 100 ], renal cell carcinoma (RCC) [ 101 ], bladder cancer [ 102 ], cervical squamous cell carcinoma(CSCC) [ 103 ], breast cancer [ 104 – 106 ], osteosarcoma [ 107 ], and non-small cell lung cancer (NSCLC) [ 108 ]. Furthermore, SLC16A1-AS1 exhibits multiple biological roles in these primary malignancies, highlighting its complexity in tumorigenesis and its potential as a tumor biomarker [ 93 – 108 ]. SLC16A1-AS1 is intricately linked to the proliferation, migration and invasion of tumor cells, and its abnormal expression is also related to the clinical characteristics and prognosis of cancer patients [ 93 – 108 ].…”

“…Furthermore, SLC16A1-AS1 exhibits multiple biological roles in these primary malignancies, highlighting its complexity in tumorigenesis and its potential as a tumor biomarker [ 93 – 108 ]. SLC16A1-AS1 is intricately linked to the proliferation, migration and invasion of tumor cells, and its abnormal expression is also related to the clinical characteristics and prognosis of cancer patients [ 93 – 108 ].…”

“…In glioblastoma, a notably aggressive form of brain tumor [ 109 – 111 ], SLC16A1-AS1 has been identified as playing a pivotal oncogenic role, as elucidated by in vitro studies. Research by Jin et al [ 93 ] revealed that in glioblastoma cells, the lncRNA SLC16A1-AS1 regulates both mature and premature forms of miR-1269. This regulation is linked to significant changes in cancer cell behaviors, including proliferation, apoptosis, migration, and invasion, indicating SLC16A1-AS1’s role as an oncogene.…”

“…SLC16A1-AS1 has emerged as a significant biomarker with diverse clinical implications and prognostic and diagnostic values across different types of cancers (Table 2 ). In glioblastoma [ 93 , 94 ], SLC16A1-AS1 consistently exhibits upregulation and is closely associated with key clinical features such as tumor size and stage, ultimately impacting overall survival. This upregulation pattern is consistently observed in 3 out of 4 studies on HCC [ 97 – 100 ].…”