A genetic polymorphism affects the risk and prognosis of renal cell carcinoma: association with follistatin-like protein 1 expression

Liu, Yan; Han, Xue; Ye, Yu; Ding, Yibo; Ni, Chong; Liu, Wenbin; Hou, Xiaomei; Li, Zixiong; Hou, Jian; Shen, Dan; Yin, Jianhua; Zhang, Hongwei; Thompson, Timothy C.; Tan, Xiaojie; Cao, Guangwen

doi:10.1038/srep26689

Cited by 19 publications

(23 citation statements)

References 31 publications

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“…Renal cell carcinoma (RCC), originates from cells in the renal cortex and is the most common type of kidney cancer in adults worldwide, with ~270,000 new cases and ~116,000 RCC-associated mortalities each year (1,2). RCC is divided into three major subtypes, including clear cell RCC (ccRCC), papillary RCC and chromophobe RCC (3).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑508 is downregulated in clear cell renal cell carcinoma and targets ZEB1 to suppress cell proliferation and invasion

Wang

et al. 2019

Exp Ther Med

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Recent studies have identified several microRNAs (miRNAs/miRs) that are dysregulated in clear cell renal cell carcinoma (ccRCC), and their dysregulation may serve important roles in the occurrence and development of ccRCC. Therefore, understanding the expression pattern and functional roles of miRNAs in ccRCC may facilitate the identification of novel therapeutic targets for the treatment of ccRCC. In the current study, reverse transcription-quantitative polymerase chain reaction was used to determine miR-508 expression levels in ccRCC tissue samples and cell lines. The cell counting kit-8 and in vitro Transwell invasion assays were used to examine the effects of miR-508 overexpression on ccRCC cell proliferation and invasion, respectively. In addition, bioinformatics analysis and dual-luciferase reporter gene assays were used to investigate the underlying mechanism of miR-508 in ccRCC cells. Furthermore, the regulatory role of miR-508 on zinc finger E-box-binding homeobox 1 (ZEB1) mRNA and protein expression in ccRCC cells was investigated using RT-qPCR and western blot analysis, respectively. Additionally, the association between miR-508 and ZEB1 expression in ccRCC tissue samples was examined. Rescue experiments were performed to determine whether the tumor suppressive effects of miR-508 may be mediated by ZEB1 in ccRCC cells. The results of the current study demonstrated that miR-508 expression was significantly downregulated in ccRCC tissue samples and cell lines. In addition, miR-508 overexpression significantly decreased the proliferation and invasion of ccRCC cells. ZEB1 was identified as a direct target gene of miR-508 in ccRCC cells and the relative expression level of ZEB1 mRNA was significantly increased in ccRCC tissue samples. Furthermore, a negative correlation between miR-508 and ZEB1 expression was identified in ccRCC tissues. ZEB1 knockdown exhibited a functional role similar to miR-508 overexpression in ccRCC cells, and restoration of ZEB1 expression significantly reversed the inhibitory effects of miR-508 on the malignant phenotype of ccRCC cells. Taken together, the results of the current study demonstrated that miR-508 may serve a tumor suppressive role in ccRCC via direct targeting of ZEB1. MiR-508 may present a novel and efficient therapeutic target for the treatment of patients with ccRCC.

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Section: Introductionmentioning

confidence: 99%

MicroRNA‑508 is downregulated in clear cell renal cell carcinoma and targets ZEB1 to suppress cell proliferation and invasion

Wang

et al. 2019

Exp Ther Med

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“…The human RCC cell lines (786-O and ACHN) were originally obtained from the American Type Culture Collection (Manassas, VA, USA). The human embryo kidney cell line 293T (293T) was purchased from the Type Culture Collection of the Chinese Academy of Medical Sciences YULIN LAI 1,2,5* , JING QUAN 1,3,5* ,CANBIN LIN 1,4,5 , HANG LI 1,5 , JIA HU 1,2 , PEIJIE CHEN 1,4,5 , JINLING XU 1,5 , XIN GUAN 1,5 , WEIJIE XU 1,5 , YONGQING LAI 1,5 and LIANGCHAO NI 1,5 (Shanghai, China). All of them were cultured in Dulbecco's modified Eagle's medium (DMEM; Invitrogen; Thermo Fisher Scientific, Inc., Waltham, MA, USA), with 10% fetal bovine serum (FBS; GE Healthcare, Little Chalfont, UK), 1% glutamine and 1% antibiotics (100 U/ml penicillin and 100 mg/ml streptomycin; Gibco; Thermo Fisher Scientific, Inc.).…”

Section: Methodsmentioning

confidence: 99%

“…Renal cell carcinoma (RCC) accounts for 3% of all malignant tumors; ~270,000 new cases are diagnosed and ~116,000 RCC-associated mortalities occur worldwide per annum (1,2). Furthermore, 25-30% of patients have already developed metastatic disease at the time-point of diagnosis (3).…”

Section: Introductionmentioning

confidence: 99%

miR‑199b‑5p serves as a tumor suppressor in renal cell carcinoma

et al. 2018

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MicroRNA (miR)-199b-5p has been reported to have a critical role in various types of malignancy. However, the exact function miR-199b-5p in renal cancer remains to be fully elucidated. The present study aimed to detect the expression levels of miR-199b-5p in renal cell carcinoma (RCC) tissues and RCC cell lines, and investigated the effect of miR-199b-5p with Cell Counting Kit-8, MTT, scratch wound, Transwell and flow cytometric assays. The results demonstrated that the expression levels of miR-199b-5p were significantly downregulated in RCC tissues and cell lines compared with those in paired adjacent normal renal tissues and a reference cell line, respectively. Downregulation of miR-199b-5p by transfection with a synthetic inhibitor promoted cellular proliferation and migration, while reducing the apoptotic rate, indicating that miR-199b-5p may serve as a tumor suppressor in RCC. Further study is required to identify target genes of miR-199b-5p to elucidate the mechanisms underlying the role of miR-199b-5p in the occurrence and development of RCC.

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“…Moreover, experimental studies have shown that FSTL1 inhibition promotes apoptotis of lung cancer cells [13]. In contrast, FSTL1 exerts tumor-suppressive actions in ovarian and endometrial carcinogenesis and its expression is down-regulated in metastatic clear-cell renal-cell carcinoma [14,15]. Recent studies have also documented altered expression of FSTL1 in human CRC, but divergent results have been provided regarding the cell sources of the cytokine and its role in the regulation of CRC cell behavior [16][17][18].…”

Section: Research Papermentioning

confidence: 99%

Follistatin-like protein 1 sustains colon cancer cell growth and survival

Bevivino¹

2017

Preprint

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Follistatin-like protein 1 (FSTL1) is a secreted glycoprotein, which controls several physiological and pathological events. FSTL1 expression is deregulated in many tumors, but its contribution to colon carcinogenesis is not fully understood. Here, we investigated the expression and functional role of FSTL1 in colorectal cancer (CRC). A significant increase of FSTL1 was seen in human CRC as compared to the surrounding non-tumor tissues and this occurred at both RNA and protein level. Knockdown of FSTL1 in CRC cells with a specific antisense oligonucleotide (AS) reduced expression of regulators of the late G1 phase, such as phosphorylated retinoblastoma protein, E2F-1, cyclin E and phospho-cyclin-dependent kinase-2, and promoted accumulation of cells in the G1 phase of the cell cycle thus resulting in diminished cell proliferation. Consistently, recombinant FSTL1 induced proliferation of normal intestinal epithelial cells through an ERK1/2-dependent mechanism. Cell cycle arrest driven by FSTL1 AS in CRC cells was accompanied by activation of caspases and subsequent induction of apoptosis. Moreover, FSTL1 knockdown made CRC cells more susceptible to oxaliplatin and irinotecan-induced death. Data indicate that FSTL1 is over-expressed in human CRC and suggest a role for this protein in favouring intestinal tumorigenesis.

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A genetic polymorphism affects the risk and prognosis of renal cell carcinoma: association with follistatin-like protein 1 expression

Cited by 19 publications

References 31 publications

MicroRNA‑508 is downregulated in clear cell renal cell carcinoma and targets ZEB1 to suppress cell proliferation and invasion

MicroRNA‑508 is downregulated in clear cell renal cell carcinoma and targets ZEB1 to suppress cell proliferation and invasion

miR‑199b‑5p serves as a tumor suppressor in renal cell carcinoma

Follistatin-like protein 1 sustains colon cancer cell growth and survival

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