J Cancer 2022; 13(9):2844-2854. doi:10.7150/jca.73758 This issue

Research Paper

LncRNA LINC00460 facilitates the proliferation and metastasis of renal cell carcinoma via PI3K/AKT signaling pathway

Feng-Juan Zhou1,4#, Sen Meng2#, Xiao-Feng Wu5#, Ping-Fu Hou2,3, Min-Le Li2,3, Su-Fang Chu2, Jin Bai2,3✉, Jun-Nian Zheng1,2,3✉

1. The Fourth Clinical College of Nanjing Medical University, Nanjing 211100, Jiangsu Province, China.
2. Cancer Institute, Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China.
3. Center of Clinical Oncology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China.
4. Department of Radiotherapy, the Second Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China.
5. Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University; Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences; NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing 210029, Jiangsu Province, China.
#These authors contributed equally to this work.

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Citation:
Zhou FJ, Meng S, Wu XF, Hou PF, Li ML, Chu SF, Bai J, Zheng JN. LncRNA LINC00460 facilitates the proliferation and metastasis of renal cell carcinoma via PI3K/AKT signaling pathway. J Cancer 2022; 13(9):2844-2854. doi:10.7150/jca.73758. Available from https://www.jcancer.org/v13p2844.htm

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Abstract

Graphic abstract

Renal cell carcinoma (RCC) is one of the most prevalent cancers diseases in the worldwide. Long noncoding RNAs (LncRNAs) have been indicated as a mediator acted in tumorigenesis of RCC. LINC00460 has been reported to participate in many kinds of malignancies and promotes cancer progressions. However, the mechanism of LINC00460 on RCC is yet to be investigated. This study aimed to explore the potential function and regulation mechanism of LINC00460 in RCC. We analysed the LINC00460 expression and the prognosis in RCC patients using Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) databases. LINC00460 level in normal renal cell line and RCC cell lines were examined by qRT-PCR. We study the effects of LINC00460 on proliferation, migration, invasion, apoptosis in RCC cells lines using a series of in vivo and in vitro experiments. RNA sequencing (RNA-seq) analysis was applied to searching potential LINC00460 related signal pathway in RCC. We identified the significant up-regulated expression of LINC00460 both in RCC tissues and cell. RCC patients with elevated LINC00460 expression have shorter survival. Up-expression of LINC00460 promoted cell proliferation, invasion and migration, meanwhile down-regulation of LINC00460 exerted inhibitory effect on these activities. We crucially identified that LNC00460 promotes development of RCC by influencing the PI3K/AKT pathway. Knockdown of LNC00460 decreased the phosphorylation of AKT and mTOR. The key finding of our study showed that LINC00460 functions as an oncogene in RCC pathogenesis by mediating the PI3K/AKT.

Keywords: RCC, LINC00460, proliferation, metastasis, PI3K/AKT pathway