SSRP1 promotes colorectal cancer progression and is negatively regulated by miR-28-5p

Wei Wu, Ke He, Qian Guo, Jingdi Chen, Mengjiao Zhang, Kai Huang, Dongmei Yang, Lu Wu, Yunchao Deng, Xu Luo, Honggang Yu, Qianshan Ding, Guoan Xiang

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

In this study, microarray data analysis, real-time quantitative PCR and immunohistochemistry were used to detect the expression levels of SSRP1 in colorectal cancer (CRC) tissue and in corresponding normal tissue. The association between structure-specific recognition protein 1 (SSRP1) expression and patient prognosis was examined by Kaplan-Meier analysis. SSRP1 was knocked down and overexpressed in CRC cell lines, and its effects on proliferation, cell cycling, migration, invasion, cellular energy metabolism, apoptosis, chemotherapeutic drug sensitivity and cell phenotype-related molecules were assessed. The growth of xenograft tumours in nude mice was also assessed. MiRNAs that potentially targeted SSRP1 were determined by bioinformatic analysis, Western blotting and luciferase reporter assays. We showed that SSRP1 mRNA levels were significantly increased in CRC tissue. We also confirmed that this upregulation was related to the terminal tumour stage in CRC patients, and high expression levels of SSRP1 predicted shorter disease-free survival and faster relapse. We also found that SSRP1 modulated proliferation, metastasis, cellular energy metabolism and the epithelial-mesenchymal transition in CRC. Furthermore, SSRP1 induced apoptosis and SSRP1 knockdown augmented the sensitivity of CRC cells to 5-fluorouracil and cisplatin. Moreover, we explored the molecular mechanisms accounting for the dysregulation of SSRP1 in CRC and identified microRNA-28-5p (miR-28-5p) as a direct upstream regulator of SSRP1. We concluded that SSRP1 promotes CRC progression and is negatively regulated by miR-28-5p.

Original languageEnglish (US)
Pages (from-to)3118-3129
Number of pages12
JournalJournal of cellular and molecular medicine
Volume23
Issue number5
DOIs
StatePublished - May 2019

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MicroRNAs
Colorectal Neoplasms
Proteins
Energy Metabolism
Apoptosis
Epithelial-Mesenchymal Transition
Kaplan-Meier Estimate
Microarray Analysis
Computational Biology
Luciferases
Heterografts
Nude Mice
Fluorouracil
Cisplatin
Disease-Free Survival
Cell Movement
Real-Time Polymerase Chain Reaction
Neoplasms
Up-Regulation
Western Blotting

Keywords

  • SSRP1
  • colorectal cancer
  • microRNA
  • progression

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

Cite this

SSRP1 promotes colorectal cancer progression and is negatively regulated by miR-28-5p. / Wu, Wei; He, Ke; Guo, Qian; Chen, Jingdi; Zhang, Mengjiao; Huang, Kai; Yang, Dongmei; Wu, Lu; Deng, Yunchao; Luo, Xu; Yu, Honggang; Ding, Qianshan; Xiang, Guoan.

In: Journal of cellular and molecular medicine, Vol. 23, No. 5, 05.2019, p. 3118-3129.

Research output: Contribution to journalArticle

Wu, W, He, K, Guo, Q, Chen, J, Zhang, M, Huang, K, Yang, D, Wu, L, Deng, Y, Luo, X, Yu, H, Ding, Q & Xiang, G 2019, 'SSRP1 promotes colorectal cancer progression and is negatively regulated by miR-28-5p', Journal of cellular and molecular medicine, vol. 23, no. 5, pp. 3118-3129. https://doi.org/10.1111/jcmm.14134
Wu, Wei ; He, Ke ; Guo, Qian ; Chen, Jingdi ; Zhang, Mengjiao ; Huang, Kai ; Yang, Dongmei ; Wu, Lu ; Deng, Yunchao ; Luo, Xu ; Yu, Honggang ; Ding, Qianshan ; Xiang, Guoan. / SSRP1 promotes colorectal cancer progression and is negatively regulated by miR-28-5p. In: Journal of cellular and molecular medicine. 2019 ; Vol. 23, No. 5. pp. 3118-3129.
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AU - Guo, Qian

AU - Chen, Jingdi

AU - Zhang, Mengjiao

AU - Huang, Kai

AU - Yang, Dongmei

AU - Wu, Lu

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AU - Luo, Xu

AU - Yu, Honggang

AU - Ding, Qianshan

AU - Xiang, Guoan

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AB - In this study, microarray data analysis, real-time quantitative PCR and immunohistochemistry were used to detect the expression levels of SSRP1 in colorectal cancer (CRC) tissue and in corresponding normal tissue. The association between structure-specific recognition protein 1 (SSRP1) expression and patient prognosis was examined by Kaplan-Meier analysis. SSRP1 was knocked down and overexpressed in CRC cell lines, and its effects on proliferation, cell cycling, migration, invasion, cellular energy metabolism, apoptosis, chemotherapeutic drug sensitivity and cell phenotype-related molecules were assessed. The growth of xenograft tumours in nude mice was also assessed. MiRNAs that potentially targeted SSRP1 were determined by bioinformatic analysis, Western blotting and luciferase reporter assays. We showed that SSRP1 mRNA levels were significantly increased in CRC tissue. We also confirmed that this upregulation was related to the terminal tumour stage in CRC patients, and high expression levels of SSRP1 predicted shorter disease-free survival and faster relapse. We also found that SSRP1 modulated proliferation, metastasis, cellular energy metabolism and the epithelial-mesenchymal transition in CRC. Furthermore, SSRP1 induced apoptosis and SSRP1 knockdown augmented the sensitivity of CRC cells to 5-fluorouracil and cisplatin. Moreover, we explored the molecular mechanisms accounting for the dysregulation of SSRP1 in CRC and identified microRNA-28-5p (miR-28-5p) as a direct upstream regulator of SSRP1. We concluded that SSRP1 promotes CRC progression and is negatively regulated by miR-28-5p.

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