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.
Highlights
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and one of the major causes of cancer mortality worldwide.[1]
structure‐ specific recognition protein 1 (SSRP1)‐ overexpressing CRC cells showed a higher rate of glycolysis and a higher mitochondrial respiratory ratio than the mock‐treated and control cells according to the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR), while SSRP1 knockdown had the inverse effect (Figure S4A,B)
Our study shows that SSRP1 promotes CRC progression, which agrees with previous studies in other types of cancers, such as nonsmall cell lung cancer,[30] breast cancer[13,31] and hepatic carcinoma (HCC).[23]
Summary
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and one of the major causes of cancer mortality worldwide.[1]. SSRP1 has been shown to induce many types of human cancers, previous studies have concentrated only on its role in stimulating proliferation by promoting cell cycle progression; its functions in metastasis and chemoresistance have rarely been investigated. Another problem to address is the mechanism underlying high SSRP1 expression in cancer tissue. We found that SSRP1 is an important oncogene in CRC, and the pathogenic up‐regulation of SSRP1 is partially attributed to the down‐regulation of miR‐28‐5p
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