Abstract
Objective: It has been shown that LIM-domain-binding protein 1 (LDB1) is involved in the tumorigenesis of several cancers, but its function in colorectal cancer (CRC) has not been fully explained. This study is aimed to investigate whether LDB1 is involved in regulating the cell growth and drug sensitivity of CRC.Methods: To analyze the protein expression of LDB1 in CRC tissues, western blot was used. KM plotter and UALCAN databases were used to predict the prognosis of CRC patients with low or high LDB1 expression. To do the correlation analysis in CRC tissues, GEPIA database was used. CCK-8 assay and xenograft models were used to evaluate the effects of LDB1 in CRC cell growth. An oxaliplatin-resistant cell line was constructed to evaluate the effect of LDB1 in drug sensitivity of CRC cells.Results: Our current research confirmed that LDB1 was upregulated in CRC tumor tissues, and its elevation predicted a poor prognosis for CRC patients. LDB1 was also found positively correlated with CCNA1, BCL2 and BCLW, but negatively correlated with the pro-apoptotic signals (BID, BAX and BAK). Silence of LDB1 significantly inhibited CRC cell growth in vitro, and CRC cells with low expression of LDB1 had a lower tumorigenesis rate in tumor-bearing nude mice. Our experiments also showed that LDB1 silence enhanced the anti-tumor activity of oxaliplatin in CRC cells. The expression of LDB1 was also found increased in oxaliplatin-resistant CRC cell lines, and silence of LDB1 partly restored the antitumor effect of oxaliplatin in an oxaliplatin-resistant CRC cell line.Conclusion: Our current results revealed the roles of LDB1 in the growth and drug resistance of CRC cells, and may provide the new theoretical support for LDB1 as a potential target for the treatment of CRC in the future.
Highlights
Colorectal cancer (CRC) is a common malignant cancer of the digestive system, which mainly occurs in the rectum and the junction of rectum and sigmoid colon, accounting for about 60% [1]
We used KM Plotter and UALCAN to assess the effect of LIM-domain-binding protein 1 (LDB1) on overall survival of CRC patients
Our present results further confirmed that LDB1 was a poor prognosis for CRC patients
Summary
Colorectal cancer (CRC) is a common malignant cancer of the digestive system, which mainly occurs in the rectum and the junction of rectum and sigmoid colon, accounting for about 60% [1]. 5-FU, platinum, irinotecan and capecitabine are the traditional chemotherapeutic drugs for CRC [4]. It is easy for CRC cells to acquire resistance to the platinum drugs and develop resistance [6]. Great progress has been made in the treatment and diagnosis of CRC [7, 8], the further improvement of the survival rate of CRC is still limited. Given these, identifying early diagnosis and prognostic markers of CRC are of great significance for guiding treatment and improving the prognosis of patients
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