Elevated Levels of Small Nucleolar RNA Predict More Aggressive Colorectal Cancer

High levels of the small nucleolar RNA SNORA42 in patients with colorectal cancer (CRC) have been shown to indicate that the patient may have a tumor that is especially aggressive, resistant to treatment, and prone to migrate and metastasize.

Small nucleolar RNA SNORA42 is a non-coding RNA (ncRNA) molecule that functions in the modification of other small nuclear RNAs (snRNAs). This type of modifying RNA, called a snoRNA, is usually located in the nucleolus of the eukaryotic cell, which is a major site of snRNA biogenesis. SNORA42 belongs to the C/D box class of snoRNAs, which contain the conserved sequence motifs known as the C box (UGAUGA) and the D box (CUGA). Most of the members of the box C/D family function in directing site-specific 2'-O-methylation of substrate RNAs.

As recent evidence had revealed a new role for snoRNAs in oncogenesis, investigators at Baylor University Medical Center (Dallas, TX, USA) systematically evaluated dysregulation of snoRNAs in CRC and clarified their biomarker potential and biological significance in CRC.

The investigators analyzed expression levels of four snoRNAs in 274 colorectal tissues from three independent cohorts and six colon cancer cell lines. The functional characterization for the role of SNORA42 in CRC was investigated through a series of in vitro and in vivo experiments.

Results revealed that SNORA42 was overexpressed in colorectal cancer cells, compared with normal tissue, and its expression significantly correlated with disease progression. Overexpression resulted in the cancer cells’ ability to multiply rapidly, form tumors, migrate, invade normal tissue, and survive apoptosis. When SNORA42 was experimentally suppressed, these effects were reversed. Elevated expression appeared to be a predictor for recurrence and poor prognosis in patients with colorectal cancer.

SNORA42 appeared to be a novel oncogene that could serve as a promising predictive biomarker for recurrence and prognosis in patients with CRC. Furthermore, snoRAs are less vulnerable than other microRNAs to biodegradation in the clinical lab setting. Their strength and stability should allow them to be studied more extensively, possibly leading to noninvasive blood or stool tests to quickly and easily detect them.

“We need predictive biomarkers that can identify patients who are at high risk for developing tumor recurrence, especially in those with stage two colorectal cancer,” said senior author Dr. Ajay Goel, director of the center for gastrointestinal cancer research and for epigenetics and cancer prevention at Baylor University Medical Center. "These experimental findings about SNORA42, if confirmed in additional studies, may become useful in clinical settings within several years."

The paper was published in the October 15, 2015, online edition of the journal Gut.

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