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Pre-45s rRNA promotes colon cancer and is associated with poor survival of CRC patients
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Pre-45s rRNA promotes colon cancer and is associated with poor survival of CRC patients
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Journal Article
Pre-45s rRNA promotes colon cancer and is associated with poor survival of CRC patients
2017
Overview
One characteristic of cancer cells is the abnormally high rate of cell metabolism to sustain their enhanced proliferation. However, the behind mechanism of this phenomenon is still elusive. Here we find that enhanced precursor 45s ribosomal RNA (pre-45s rRNA) is one of the core mechanisms in promoting the pathogenesis of colorectal cancer (CRC).
Pre-45s rRNA
expression is significantly higher in primary CRC tumor tissues samples and cancer cell lines compared with the non-tumorous colon tissues, and is associated with tumor sizes. Knockdown of
pre-45s rRNA
inhibits G1/S cell-cycle transition by stabilizing p53 through inducing murine double minute 2 (MDM2) and ribosomal protein L11 (RpL11) interaction. In addition, we revealed that high rate of cancer cell metabolism triggers the passive release of calcium ion from endoplasmic reticulum to the cytoplasm. The elevated calcium ion in the cytoplasm activates the signaling cascade of calcium/calmodulin-dependent protein kinase II, ribosomal S6 kinase (S6K) and ribosomal S6K (CaMKII-S6K-UBF). The activated UBF promotes the transcription of
rDNA
, which therefore increases
pre-45s rRNA
. Disruption of CaMKII-S6K-UBF axis by either
RNAi
or pharmaceutical approaches leads to reduction of
pre-45s rRNA
expression, which subsequently suppresses cell proliferation in colon cancer cells by causing cell-cycle arrest. Knockdown of
APC
activates CaMKII-S6K-UBF cascade and thus enhances
pre-45s rRNA
expression. Moreover, the high expression level of
pre-45s rRNA
is associated with poor survival of CRC patients in two independent cohorts. Our study identifies a novel mechanism in CRC pathogenesis mediated by
pre-45s rRNA
and a prognostic factor of
pre-45s rRNA
in CRC patients.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 42/109
/ 82/80
/ Aged
/ Ca2+/calmodulin-dependent protein kinase II
/ Calcium-Calmodulin-Dependent Protein Kinase Type 2 - genetics
/ Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism
/ Cell Proliferation - genetics
/ Colorectal Neoplasms - genetics
/ Colorectal Neoplasms - pathology
/ Female
/ Gene Expression Regulation, Neoplastic
/ Humans
/ Kinases
/ Male
/ Medicine
/ Oncology
/ Original
/ Pol1 Transcription Initiation Complex Proteins - genetics
/ Pol1 Transcription Initiation Complex Proteins - metabolism
/ Protein Interaction Maps - genetics
/ Proto-Oncogene Proteins c-mdm2 - genetics
/ Ribosomal Protein S6 Kinases, 70-kDa - genetics
/ Ribosomal Protein S6 Kinases, 70-kDa - metabolism
/ Ribosomal Proteins - genetics
/ RNA
/ rRNA 45S
