Abstract
Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis. However, the mechanisms of most lncRNAs in cancers are largely unknown. Because the RNA component of mitochondrial RNA processing endoribonuclease (RMRP) is one of the dysregulated lncRNAs in gastric cancer, this study explored its molecular mechanisms in carcinogenesis. RMRP levels in 792 tissues, plasma and gastric juices from patients with various stages of gastric tumorigenesis were analyzed by quantitative reverse transcription-polymerase chain reaction. Overexpression and RNA interference were used to manipulate RMRP expression by RMRP expression vector and small interfering RNAs, respectively. Its mechanisms were evaluated by flow cytometry, real-time cell analysis, plate colony formation assays, and xenograft models. RMRP levels in tissue, plasma and gastric juices from patients with gastric cancer were significantly different from those from controls. Its levels were significantly associated with Borrmann type and metastasis. Plasma and gastric juice RMRP had higher sensitivity and specificity than commonly used markers (such as carcinoembryonic antigen and carbohydrate antigen 19–9). Knockdown of RMRP significantly inhibited cell proliferation in vitro and in vivo, whereas overexpression of RMRP promoted cell growth. Acting as a miR-206 sponge, RMRP modulated cell cycle by regulating Cyclin D2 expression. RMRP plays a crucial role in gastric cancer occurrence and can be used as a novel biomarker for gastric cancer.
Highlights
Gastric cancer remains the fourth most prevalent type of malignant tumor and the second leading cause of global cancer-related deaths [1,2,3]
We further explored its levels in gastric dysplasia tissues
RNA component of mitochondrial RNA processing endoribonuclease (RMRP) expression was significantly downregulated in gastric dysplasia and gastric cancer tissues
Summary
Gastric cancer remains the fourth most prevalent type of malignant tumor and the second leading cause of global cancer-related deaths [1,2,3]. RMRP is primarily identified in the nucleus, nucleolus and mitochondria [8, 9]. It is highly expressed in a wide range of human tissues and is essential for development at early stages of embryogenesis [10]. RMRP carries out an www.impactjournals.com/oncotarget essential function in the final step of 5.8S rRNA processing [12]. It interacts with the telomerase-associated reverse transcriptase (TERT) catalytic subunit to form a complex and produces double-stranded RNAs (dsRNAs), which are processed into small interfering RNA (siRNA) by Dicer [13]. Despite the above-mentioned knowledge, the roles of RMRP in pathological processes, especially in carcinogenesis, remain unknown
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