Cancer cells exploit an orphan RNA to drive metastatic progression

Abstract

In this study we performed a systematic search to identify breast cancer-specific small non-coding RNAs, which we have collectively termed orphan non-coding RNAs (oncRNAs). We subsequently discovered that one of these oncRNAs, which originates from the 3’ end of TERC, acts as a regulator of gene expression and is a robust promoter of breast cancer metastasis. This oncRNA, which we have named T3p, exerts its pro-metastatic effects by acting as an inhibitor of RISC complex activity and increasing the expression of the pro-metastatic genes NUPR1 and PANX2. Furthermore, we have shown that oncRNAs are present in cancer cell-derived extracellular vesicles, raising the possibility that these circulating oncRNAs may also play a role in non-cell autonomous disease pathogenesis. Additionally, these circulating oncRNAs present a novel avenue for cancer fingerprinting using liquid biopsies.

Emerging roles of novel small non-coding regulatory RNAs in immunity and cancer

“…With advances in technology and experimental approaches, we are beginning to appreciate the variety of small ncRNAs derived from tRNA and other long ncRNAs that can tune gene expression and protein biogenesis in a cell-and tissue-specific manner, and the precision by which stress and other signals are coordinated to induce their biogenesis. With the development of next generation sequencing technologies, the repertoire of regulatory small ncRNAs derived from other RNAs is growing 116,117 and it will be fully uncovered in the near future. Improved understanding of their functions will provide valuable insights into human physiology and pathology.…”

Novel insights into the emerging roles of tRNA-derived fragments in mammalian development

“…As such, it is possible that tRFs may thusly exchange information between different cell populations within the stem cell niche and the cancer microenvironment. Additional intriguing developments illustrate that other species of ncRNAs are fragmented into functional small ncRNAs that can also be secreted into extracellular vesicles and may have a role in cancer progression and stem cell differentiation [91]. Interestingly, tRF levels are associated with disease progression in some cancer types [92]; however, the therapeutic potential of these small RNAs remains mostly unexplored.…”

The cancer exosomes: Clinical implications, applications and challenges

“…Tumor‐related exosome regulates the tumor metastasis, and this function mainly depends on exosomal RNA. Fish et al . performed a systematic search to identify breast cancer‐specific small noncoding RNAs, which drove the metastasis of cancer cells existed in extracellular vehicles mightily.…”

“…20 Tumor-related exosome regulates the tumor metastasis, and this function mainly depends on exosomal RNA. Fish et al 21 performed a systematic search to identify breast cancer-specific small noncoding RNAs, which drove the metastasis of cancer cells existed in extracellular vehicles mightily. Wang et al 22 sequenced exosomal circular RNA (circRNA) and assumed that circPTGR1 in exosomes regulated higher metastatic hepatocellular carcinoma (HCC) cells to confer metastasis potential on lower or no metastatic potential, resulting in increasing their migratory and invasive abilities ( Table 1).…”