RRS1 silencing suppresses colorectal cancer cell proliferation and tumorigenesis by inhibiting G2/M progression and angiogenesis

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.

Functional role of RRS1 in breast cancer cell proliferation

“…Furthermore, RRS1 knockdown induced cell apoptosis. In addition to our results, the functional role of RRS1 in human colorectal and hepatocellular carcinomas has also been reported . Both papers conclude that RRS1 plays important roles in the proliferation of human cancers.…”

“…| 6311 of RRS1 in human colorectal and hepatocellular carcinomas has also been reported. 19,20 Both papers conclude that RRS1 plays important roles in the proliferation of human cancers.…”

“…The mammalian RRS1 protein is localized to both the nucleolus and the endoplasmic reticulum and is involved in the endoplasmic reticulum stress response in Huntington disease . Most importantly, RRS1 expression has been recently reported in human cancers, including human colorectal and hepatocellular carcinomas . However, the functional role of RRS1 in breast cancer and the mechanistic details of how RRS1 performs this function are currently unknown.…”

“…18 Most importantly, RRS1 expression has been recently reported in human cancers, including human colorectal and hepatocellular carcinomas. 19,20 However, the functional role of RRS1 in breast cancer and the mechanistic details of how RRS1 performs this function are currently unknown.…”

Spaceflight/microgravity inhibits the proliferation of hematopoietic stem cells by decreasing Kit‐Ras/cAMP‐CREB pathway networks as evidenced by RNA‐Seq assays

“…The cell cycle was analyzed in the collected cells using flow cytometry (25). A total of 1 × 10 6 cells were collected, washed twice using cold PBS, and then fixed in 70% ethanol overnight at 4°C The ethanol was discarded, and the cells were washed twice with PBS, followed by the addition of 50 µg/ml propidium iodide and 2% Triton X‐100 for 30 min at 4°C The DNA content was then tested using FACSCalibur flow cytometer (BD Biosciences).…”