Oncol Rep.2021 Sep;46(3):187.doi: 10.3892/or.2021.8138. Epub 2021 Jul 19.

Mechanism of tumor‑derived extracellular vesicles in regulating renal cell carcinoma progression by the delivery of MALAT1

Chengluo Jin  1 Linmei Shi  2 Kunlun Li  1 Wei Liu  1 Yu Qiu  1 Yakun Zhao  1 Bai Zhao  1 Zhexun Li  1 Yifei Li  1 Qingguo Zhu  1 Affiliations

Free PMC article

Abstract

Renal cell carcinoma (RCC) is a major healthcare burden globally. Tumor‑derived extracellular vesicles (EVs) contribute to the formation of a pro‑metastatic microenvironment. In the present study, we explored the role and mechanism of RCC cell 786‑O‑derived EVs (786‑O‑EVs) in RCC. First, 786‑O‑EVs were extracted and identified, and EV internalization of RCC cells was observed. RCC cell malignant behaviors and long noncoding RNA (lncRNA) metastasis‑associated lung adenocarcinoma transcript 1 (MALAT1) expression patterns were detected before and after 786‑O‑EV treatment. MALAT1 was intervened to evaluate RCC cell behaviors. The downstream mechanism involving MALAT1 was predicted. In addition, the relationship among MALAT1, transcription factor CP2 like 1 (TFCP2L1) and ETS proto‑oncogene 1, transcription factor (ETS1) was analyzed. TFCP2L1 expression patterns were measured after 786‑O‑EV exposure. Tumor xenograft formation assay and lung metastasis model were adopted to verify the role of 786‑O‑EVs in vivo in RCC. It was found that 786‑O‑EVs could be internalized by RCC cells. 786‑O‑EVs promoted RCC cell malignant behaviors, accompanied by elevated MALAT1 expression levels. The 786‑O‑EVs with MALAT1 knockdown attenuated the promotive effect of sole 786‑O‑EVs on RCC cells. MALAT1 located ETS1 in the TFCP2L1 promoter and negatively regulated TFCP2L1, and ETS1 protein could specifically bind to MALAT1. 786‑O‑EVs enhanced the binding of ETS1 and the TFCP2L1 promoter and decreased TFCP2L1 expression. In vivo, 786‑O‑EVs promoted tumor growth and RCC lung metastasis, which was suppressed following inhibition of MALAT1. Our findings indicated that 786‑O‑EVs promoted RCC invasion and metastasis by transporting MALAT1 to promote the binding of transcription factor ETS1 and TFCP2L1 promoter.

Keywords: ETS1; TFCP2L1; extracellular vesicles; invasion; lncRNA MALAT1; migration; renal cell carcinoma.

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