ELOVL2 promotes cancer progression by inhibiting cell apoptosis in renal cell carcinoma
ELOVL2 promotes cancer progression by inhibiting cell apoptosis in renal cell carcinoma
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DOI：
10.3892/or.2021.8234
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发表时间：
2022-02-01
期刊：
影响因子：
4.2
通讯作者：
Nishiyama, Hiroyuki
中科院分区：
文献类型：
--
作者：
Tanaka, Ken;Kandori, Shuya;Nishiyama, Hiroyuki
肾细胞癌（Renal cell carcinoma， RCC）是一种侵袭性泌尿生殖系统恶性肿瘤，预后较差，尤其是伴有转移的患者，其主要亚型为透明细胞癌（clear cell RCC, ccRCC）、乳头状肾细胞癌（papillarypccc, pRCC）和憎色细胞癌（chromophober RCC, chRCC）。细胞内脂滴（ld）的存在被认为是ccRCC的标志。脂质代谢改变在ccRCC中的重要性已被广泛认识。超长链脂肪酸（ELOVL）的延伸催化脂肪酸（FAs）的延伸，调节脂质组成，是正常身体功能所必需的。然而，延长酶在肾细胞癌中的作用尚不清楚。本研究检测ELOVL2在ccRCC中的表达；特别是，在原发肿瘤中观察到高水平的七种ELOVL同工酶。值得注意的是，在ccRCC以及pRCC和chRCC中观察到ELOVL2表达水平升高。此外，较高水平的ELOVL2与ccRCC和pRCC患者预后不良发生率的增加显著相关。CRISPR/ cas9介导的ELOVL2的敲低导致肾癌细胞长链多不饱和FAs的延伸受到抑制，LD的产生增加。此外，ELOVL2消融术在体外通过诱导细胞凋亡抑制细胞增殖，在体内通过抑制肿瘤生长。总的来说，本研究对涉及脂质代谢的肿瘤增殖机制提供了新的认识，并提示ELOVL2可能是RCC治疗的一个有吸引力的新靶点。
Renal cell carcinoma (RCC) is an aggressive genitourinary malignancy which has been associated with a poor prognosis, particularly in patients with metastasis, its major subtypes being clear cell RCC (ccRCC), papillary PCC (pRCC) and chromophobe RCC (chRCC). The presence of intracellular lipid droplets (LDs) is considered to be a hallmark of ccRCC. The importance of an altered lipid metabolism in ccRCC has been widely recognized. The elongation of very-long-chain fatty acid (ELOVL) catalyzes the elongation of fatty acids (FAs), modulating lipid composition, and is required for normal bodily functions. However, the involvement of elongases in RCC remains unclear. In the present study, the expression of ELOVL2 in ccRCC was examined; in particular, high levels of seven ELOVL isozymes were observed in primary tumors. Of note, elevated ELOVL2 expression levels were observed in ccRCC, as well as in pRCC and chRCC. Furthermore, a higher level of ELOVL2 was significantly associated with the increased incidence of a poor prognosis of patients with ccRCC and pRCC. The CRISPR/Cas9-mediated knockdown of ELOVL2 resulted in the suppression of the elongation of long-chain polyunsaturated FAs and increased LD production in renal cancer cells. Moreover, ELOVL2 ablation resulted in the suppression of cellular proliferation via the induction of apoptosis in vitro and the attenuation of tumor growth in vivo. On the whole, the present study provides new insight into the tumor proliferation mechanisms involving lipid metabolism, and suggests that ELOVL2 may be an attractive novel target for RCC therapy.