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RNF20 Suppresses Tumorigenesis by Inhibiting the SREBP1c-PTTG1 Axis in Kidney Cancer.

ABSTRACT: Elevated lipid metabolism promotes cancer cell proliferation. Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancers, characterized by ectopic lipid accumulation. However, the relationship between aberrant lipid metabolism and tumorigenesis in ccRCC is not thoroughly understood. Here, we demonstrate that ring finger protein 20 (RNF20) acts as a tumor suppressor in ccRCC. RNF20 overexpression repressed lipogenesis and cell proliferation by inhibiting sterol regulatory element-binding protein 1c (SREBP1c), and SREBP1 suppression, either by knockdown or by the pharmacological inhibitor betulin, attenuated proliferation and cell cycle progression in ccRCC cells. Notably, SREBP1c regulates cell cycle progression by inducing the expression of pituitary tumor-transforming gene 1 (PTTG1), a novel target gene of SREBP1c. Furthermore, RNF20 overexpression reduced tumor growth and lipid storage in xenografts. In ccRCC patients, RNF20 downregulation and SREBP1 activation are markers of poor prognosis. Therefore, RNF20 suppresses tumorigenesis in ccRCC by inhibiting the SREBP1c-PTTG1 axis.

SUBMITTER: Lee JH

PROVIDER: S-EPMC5660462 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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RNF20 Suppresses Tumorigenesis by Inhibiting the SREBP1c-PTTG1 Axis in Kidney Cancer.

Lee Jae Ho JH Jeon Yong Geun YG Lee Kyoung-Hwa KH Lee Hye Won HW Park Jeu J Jang Hagoon H Kang Minyong M Lee Hye Sun HS Cho Hee Jin HJ Nam Do-Hyun DH Kwak Cheol C Kim Jae Bum JB

Molecular and cellular biology 20171027 22

Elevated lipid metabolism promotes cancer cell proliferation. Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancers, characterized by ectopic lipid accumulation. However, the relationship between aberrant lipid metabolism and tumorigenesis in ccRCC is not thoroughly understood. Here, we demonstrate that ring finger protein 20 (RNF20) acts as a tumor suppressor in ccRCC. RNF20 overexpression repressed lipogenesis and cell proliferation by inhibiting sterol regulator ...[more]

PMID: 28827316

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Project description:BackgroundEmerging evidence suggested that long intergenic noncoding RNA (lincRNA) 00887 (NR_024480) reduced the invasion and metastasis of non-small cell lung cancer by sponging miRNAs degradation. However, the role and regulatory mechanism of linc00887 in the progression of cervical cancer remain largely unknown.MethodsIn vivo or vitro, RT-qPCR assay was used to detect the expression of linc00887 in human normal (N = 30), cervical cancer tissues (N = 30), human normal cervical epithelial cells (Ect1/E6E7) and cervical cancer cell lines (HeLa, C33A). Then, CCK-8 and Transwell assays were used to examine cell proliferation and invasion when linc00887 was overexpressed or knocked down. In addition, bioinformatics, luciferase reporter gene and pull-down assays were used to predict and validate the relationship between linc00887 and miR-454-3p. Moreover, we detected the expression of miR-454-3p in Ect1/E6E7, HeLa and C33A cells when linc00887 was overexpressed or knocked down. Cell proliferation and invasion were also measured when pcDNA-linc00887 and miR-454-3p were transfected alone or together. Next, miR-454-3p target gene was predicted and validated by bioinformatics and luciferase reporter gene assays. Gain- and loss-of-function experiments were performed in HeLa cells to evaluate the effect of miR-454-3p or linc00887 on the expression of FERM domain containing protein 6 (FRMD6) protein and several key proteins in the FRMD6-Hippo signaling pathway.ResultsLinc00887 was downregulated in cervical cancer tissues or human cervical cancer cell lines (Hela, C33A) compared with normal tissues or cell lines. Overexpression of linc00887 inhibited proliferation and invasion HeLa and C33A cells, while linc00887 knockdown had the opposite effect. Linc00887 bound with miR-454-3p, and overexpression of miR-454-3p rescued linc00887-induced inhibition proliferation and invasion of HeLa cells. MiR-454-3p targeted and suppressed the expression of FRMD6, and linc00887 suppressed tumorigenesis of cervical cancer through activating the FRMD6-Hippo signaling pathway.ConclusionsLinc00887, sponging miR-454-3p, inhibited the progression of cervical cancer by activating the FRMD6-Hippo signaling pathway.

Dataset Information

RNF20 Suppresses Tumorigenesis by Inhibiting the SREBP1c-PTTG1 Axis in Kidney Cancer.

Publications

RNF20 Suppresses Tumorigenesis by Inhibiting the SREBP1c-PTTG1 Axis in Kidney Cancer.

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