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Published on: August 12, 2015
RRS1 silencing suppresses colorectal cancer cell proliferation and tumorigenesis by inhibiting G2/M progression and
Xin-Lin Wu1, Zhi-Wen Yang1, Li He1
1Department of Gastrointestinal Surgery, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010059, Inner Mongolian Autonomous Region, China.
Abstract:
Colorectal cancer (CRC) is one of the most common malignancies worldwide. Ribosome biogenesis regulatory protein homolog (RRS1) is an essential factor involved in ribosome biogenesis, while its role in CRC remains largely unclear. Here, we found that RRS1 expression was significantly higher in CRC tissues compared with adjacent normal tissues. RRS1 High expression also predicted poor overall survival of CRC patients. Knockdown of RRS1 induced the G2/M cell cycle arrest, apoptosis and suppressed the proliferation of RKO and HCT-116 CRC cells. Furthermore, angiogenesis was also reduced in CRC cells after RRS1 knockdown. In addition, suppression of RRS1 blunted the tumor formation of CRC cells in nude mice. At the molecular level, silencing of RRS1 decreased the expression of M-phase inducer phosphatase 3 (CDC25C), Cyclin-dependent kinase 1 (CDK1), antigen KI-67 (KI67) and increased the protein level of cyclin-dependent kinase inhibitor 1 (CDKN1A) and tumor suppressor p53 (p53). Taken together, our findings provide evidence that RRS1 may promote the development of colon cancer. Therefore, targeting RRS1 may be a promising therapeutic strategy for CRC patients.
Insights
Ribosome biogenesis regulatory protein homolog (RRS1) is overexpressed in colorectal cancer (CRC), promoting tumor growth and poor survival. Targeting RRS1 may offer a new therapeutic strategy for CRC patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Colorectal cancer (CRC) is a leading global malignancy.
- The role of Ribosome biogenesis regulatory protein homolog (RRS1) in CRC is not well understood.
- RRS1 is crucial for ribosome biogenesis.
Purpose of the Study:
- To investigate the role of RRS1 in colorectal cancer development and progression.
- To explore RRS1 as a potential therapeutic target for CRC.
Main Methods:
- Analysis of RRS1 expression in CRC tissues and correlation with patient survival.
- In vitro studies involving RRS1 knockdown in CRC cell lines (RKO, HCT-116) to assess effects on cell cycle, apoptosis, proliferation, and angiogenesis.
- In vivo tumor formation assays in nude mice.
- Molecular analysis of key cell cycle regulators (CDC25C, CDK1, KI67, CDKN1A, p53).
Main Results:
- RRS1 expression is significantly elevated in CRC tissues and linked to poorer patient survival.
- RRS1 knockdown induced G2/M cell cycle arrest, apoptosis, and suppressed proliferation and angiogenesis in CRC cells.
- RRS1 suppression reduced tumor formation in vivo.
- Silencing RRS1 altered the expression of cell cycle regulators, including decreased CDC25C, CDK1, KI67 and increased CDKN1A, p53.
Conclusions:
- RRS1 promotes colorectal cancer development and progression.
- RRS1 is a potential prognostic biomarker and therapeutic target for CRC.
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