Role of long non‑coding RNA leucine‑rich repeat containing 75 A‑antisense RNA1 in the invasion and progression of renal cell carcinoma

含75A反义RNA1的长链非编码RNA亮氨酸富集重复序列在肾细胞癌侵袭和进展中的作用

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作者:Takanori Tokunaga, Hiroshi Hirata, Yukihiro Hitaka, Nakanori Fujii, Keita Kobayashi, Takahide Hayano, Yoshiyuki Asai, Koji Shiraishi

Abstract

Long noncoding RNAs (lncRNAs) serve pivotal roles in cancer biology. The present study investigated the oncogenic roles of lncRNAs in renal cell carcinoma (RCC) and their potential as prognostic biomarkers. The lncRNA leucine‑rich repeat containing 75 A‑antisense RNA1 (LRRC75A‑AS1) was identified through lncRNA microarray as a potential lncRNA that may predict the efficacy of immune checkpoint inhibitor therapy and cancer progression in RCC. The present study subsequently assessed the expression of LRRC75A‑AS1 in 212 patients with clear cell RCC (ccRCC) who underwent nephrectomy, and performed in vitro functional analysis of LRRC75A‑AS1 in RCC cell lines. Additionally, the interactions between LRRC75A‑AS1, microRNA (miR)‑370‑5p and ADAMTS5 were explored. LRRC75A‑AS1 was revealed to be significantly upregulated in ccRCC tissues compared with in adjacent normal tissues, and high LRRC75A‑AS1 expression was associated with poor prognosis, including lower progression‑free survival, in patients with RCC. The knockdown of LRRC75A‑AS1 in RCC cell lines resulted in reduced cell proliferation and invasion, highlighting its role in promoting tumorigenesis. Furthermore, the interaction among LRRC75A‑AS1, miR‑370‑5p and ADAMTS5 was suggested as a regulatory mechanism underlying RCC progression. These findings indicated that LRRC75A‑AS1 may function as an oncogene in RCC, promoting cell proliferation and invasion. Its significant upregulation in ccRCC tissues and association with poor prognosis underscore its potential as a prognostic biomarker for RCC. Understanding the regulatory interactions among LRRC75A‑AS1, miR‑370‑5p and ADAMTS5 may provide new insights into the molecular mechanisms underlying RCC and facilitate the identification of novel therapeutic targets.

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