Telomeric Repeat-Containing RNAs (TERRA) Decrease in Squamous Cell Carcinoma of the Head and Neck Is Associated with Worsened Clinical Outcome

Abstract

Telomeres are transcribed into noncoding telomeric repeat-containing RNAs (TERRA), which are essential for telomere maintenance. Deregulation of TERRA transcription impairs telomere metabolism and a role in tumorigenesis has been proposed. Head and neck cancer (HNC) is one of the most frequent cancers worldwide, with head and neck squamous cell carcinoma (HNSCC) being the predominant type. Since HNSCC patients are characterized by altered telomere maintenance, a dysfunction in telomere transcription can be hypothesized. In this prospective study, we compared TERRA levels in the tumor and matched normal tissue from 23 HNSCC patients. We then classified patients in two categories according to the level of TERRA expression in the tumor compared to the normal tissue: (1) lower expression in the tumor, (2) higher or similar expression in tumor. A significant proportion of patients in the first group died of the disease within less than 34 months postsurgery, while the majority of patients in the second group were alive and disease-free. Our results highlight a striking correlation between TERRA expression and tumor aggressiveness in HNSCC suggesting that TERRA levels may be proposed as a novel molecular prognostic marker for HNSCC.

Noncoding telomeric repeat‐containing RNA inhibits the progression of hepatocellular carcinoma by regulating telomerase‐mediated telomere length

“…Growing evidence has shown that the dysregulation of TERRA has been implicated in many types of cancers, such as osteosarcoma, medulloblastoma, stomach adenocarcinoma, head and neck cancer, and cervical carcinoma 12‐15,27,28 . However, the functional role of TERRA in hepatocarcinogenesis is largely unknown.…”

“…Furthermore, the deregulation of TERRA transcription has been proved to impair the telomere and contribute to tumorigenesis. For example, head and neck squamous cell carcinoma patients with low‐level expression of TERRA have poorer clinical outcomes than patients with high‐level expression of TERRA 13 . In addition, the expression of TERRA is downregulated in malignant glioma tissues and negatively correlated with advanced clinical grade 14 .…”

“…*P < .05; **P < .01. shCtrl, control shRNA vector; shTRF1 or shTRF2, shRNA vector against TTAGGG repeat binding factor (TRF)1 or TRF2; siCtrl, control siRNA; siTERRA, siRNA against TERRA medulloblastoma, stomach adenocarcinoma, head and neck cancer, and cervical carcinoma. [12][13][14][15]27,28 However, the functional role of TERRA in hepatocarcinogenesis is largely unknown. In this study, the expression levels of TERRA and its regulators (TRF1 and TRF2) were investigated in HCC.…”

“…Telomeric repeat‐containing RNA has been found to be closely related to tumorigenesis. The expression level of TERRA was frequently downregulated in various types of tumor tissues compared with normal tissues 12‐14 . In contrast, TERRA is upregulated and significantly associated with poor prognosis of patients with medulloblastoma 15 .…”

“…The expression level of TERRA was frequently downregulated in various types of tumor tissues compared with normal tissues. [12][13][14] In contrast, TERRA is upregulated and significantly associated with poor prognosis of patients with medulloblastoma. 15 These findings indicate that the expression level of TERRA varies during tumor progression, possibly in a tumor type-specific manner.…”