Upregulation of MIAT Regulates LOXL2 Expression by Competitively Binding MiR-29c in Clear Cell Renal Cell Carcinoma

Abstract

Background/Aims: MIAT is a long noncoding RNA (lncRNA) involved in cell proliferation and the development of tumor. However, the exact effects and molecular mechanisms of MIAT in clear cell renal cell carcinoma (ccRCC) progression are still unknown. Methods: We screened the lncRNAs’ profile of ccRCC in The Cancer Genome Atlas database, and then examined the expression levels of lncRNA MIAT in 45 paired ccRCC tissue specimens and in cell lines by q-RT-PCR. MTS, colony formation, EdU, and Transwell assays were performed to examine the effect of MIAT on proliferation and metastasis of ccRCC. Western blot and luciferase assays were performed to determine whether MIAT can regulate Loxl2 expression by competitively binding miR-29c in ccRCC. Results: MIAT was up-regulated in ccRCC tissues and cell lines. High MIAT expression correlated with worse clinicopathological features and shorter survival rate. Functional assays showed that knockdown of MIAT inhibited renal cancer cell proliferation and metastasis in vitro and in vivo. Luciferase and western blot assays further confirmed that miR-29c binds with MIAT. Additionally, the correlation of miR-29c with MIAT and Loxl2 was further verified in patients' samples. Conclusion: Our data indicated that MIAT might be an oncogenic lncRNA that promoted proliferation and metastasis of ccRCC, and could be a potential therapeutic target in human ccRCC.

RNA sequencing reveals a key role for the long non-coding RNA MIAT in regulating neuroblastoma and glioblastoma cell fate

“…Similarly to our sequencing, prior functional annotation had implied that MIAT is associated with EMT-related canonical pathways in hepatocellular carcinoma cells [47], including the TGF-β pathway, justifying the perturbations in this pathway following the perturbation in MIAT expression in our study. Furthermore, consistent with other studies reporting that MIAT is involved in cell migration and invasion and its downregulation inhibits this effect in other cancer types, for example in NSCLC (non-small-cell lung cancer) [48], colorectal cancer [49], clear cell renal cell carcinoma [50] and breast cancer [51], our results reveal that the ability of neuroblastoma and GBM cells to migrate is as well inhibited to an important extent when MIAT is knocked down. Given that cell migration comprises one of the first steps towards tumour metastasis, MIAT downregulation could be a potent therapeutic approach towards the prevention of metastasis .…”

Lysyl Oxidase Like‐2 (LOXL2): An Emerging Oncology Target

“…In both cell lines, LOXL2 expression was significantly reduced with treatment of mi‐R29 . Similar results were obtained relating the LOXL2 expression to the restoration of mi‐R26s function. These findings highlight a compelling pathway linking LOXL2 with mi‐RNAs in cancer metastasis and its underlying biology; essential for understanding the mechanism of LOXL2 action in cancer.…”

“…As with NSCLC data, the mi‐R29 family have been identified in ccRCC, maintaining the same role; restoring levels inhibits migration . Quantitative RT‐PCR and western blotting conducted on kidney cancer cells, 786‐O and A498 lines assessed the effects on LOXL2 expression.…”

“…Clear cell renal carcinoma (ccRCC) is the most common form of renal cancer, accounting for 80% of all cases . At diagnosis, around 30% of renal carcinomas have already metastasized and neither radiotherapy nor chemotherapy is used for treatment.…”

LncRNA MIAT facilitates osteosarcoma progression by regulating mir‐128‐3p/VEGFC axis

“…Among those lncRNAs, MIAT, a novel lncRNA, was found to be dysregulated and to promote malignancy in various cancers. In clear cell renal cell carcinoma (ccRCC), MIAT was over‐expressed and high expression of MIAT was associated with poor prognosis in ccRCC patients . In breast cancer, MIAT was obviously up‐regulated and its inhibition induced senescence in breast cancer cells in vitro .…”