The Function of Non-Coding RNAs in Lung Cancer Tumorigenesis

Abstract

Lung cancer is the most prevalent and deadliest cancer worldwide. A significant part of lung cancer studies is dedicated to the expression alterations of non-coding RNAs. The non-coding RNAs are transcripts that cannot be translated into proteins. While the study of microRNAs and siRNAs in lung cancer received a lot of attention over the last decade, highly efficient therapeutic option or the diagnostic methods based on non-coding RNAs are still lacking. Because of this, it is of utmost importance to direct future research on lung cancer towards analyzing other RNA types for which the currently available data indicates that are essential at modulating lung tumorigenesis. Through our review of studies on this subject, we identify the following non-coding RNAs as tumor suppressors: ts-46, ts-47, ts-101, ts-53, ts-3676, ts-4521 (tRNA fragments), SNORD116-26, HBII-420, SNORD15A, SNORA42 (snoRNAs), piRNA-like-163, piR-35127, the piR-46545 (piRNAs), CHIAP2, LOC100420907, RPL13AP17 (pseudogenes), and uc.454 (T-UCR). We also found non-coding RNAs with tumor-promoting function: tRF-Leu-CAG, tRNA-Leu, tRNA-Val (tRNA fragments), circ-RAD23B, circRNA 100146, circPVT1, circFGFR3, circ_0004015, circPUM1, circFLI1, circABCB10, circHIPK3 (circRNAs), SNORA42, SNORA3, SNORD46, SNORA21, SNORD28, SNORA47, SNORD66, SNORA68, SNORA78 (snoRNAs), piR-65, piR-34871, piR-52200, piR651 (piRNAs), hY4 5' fragments (YRNAs), FAM83A-AS1, WRAP53, NKX2-1-AS1 (NATs), DUXAP8, SFTA1P (pseudogene transcripts), uc.338, uc.339 (T-UCRs), and hTERC.

Keywords: T-UCR; YRNA; circRNA; lung cancer; ncRNA; piRNA; snoRNA.

Figure 1

Graphic representation of the MeSH (PubMed comprehensive controlled vocabulary), results, by using the keywords “Lung Neoplasms” (MeSH)) and “RNA, Untranslated” (MeSH), from 5008 (date of access: 25.03.2019), we included in our brief analysis 2977 articles specific for our subject. More than 65% of studies (meaning 1925 articles from a total of 2977 investigated articles (based on MeSH vocabulary, “Lung Neoplasms” [Mesh] AND “RNA, Untranslated” [Mesh]), including original articles, reviews, and meta-analysis) analyzed the implication of various miRNAs in lung cancer (excluding studies which included the axis lncRNAs-miRNAs-mRNAs). At the same time, 21% of the current literature (meaning 641 articles from a total of 2977 investigated articles, including original articles, reviews and meta-analysis) have included siRNAs as a therapeutic option (from the total number of siRNAs studies we excluded the ones who had as their main subject the study of miRNAs). The “classic” lncRNAs (which includes a high heterogeneity of transcripts) are on the third place, comprising 13% of the total number of studies (377 out of 2977). CircRNAs are in the fourth place, but their number has continuously increased over the last year (20 studies from 2977). The lesser studied non-coding RNAs (snoRNAs, hTERC, tRNAs, piRNAs, pseudogene transcripts and T-UCRs) comprise only 0.47% of articles which analyze the role of non-coding RNAs in lung cancer; however, they are involved in various and multi-level molecular processes.

Figure 2

The lesser-known non-coding RNAs in lung cancer. The following non-coding RNAs function as tumor suppressors: ts-46, ts-47, ts-101, ts-53, ts-3676, ts-4521 (tRNA fragments), SNORD116-26, HBII-420, SNORD15A, SNORA42 (snoRNAs), piRNA-like-163, piR-35127, the piR-46545 (piRNA), CHIAP2, LOC100420907, RPL13AP17 (pseudogenes), and Uc.454 (T-UCR). The oncogenic non-coding RNAs from the above mentioned categories are: tRF-Leu-CAG, tiRNAs-Leu, tiRNAs-Val (tRNA fragments), circ-RAD23B, circRNA 100146, circPVT1, circFGFR3, circ_0004015, circPUM1, circFLI1, circABCB10, circHIPK3 (circRNAs), SNORA42, SNORA3, SNORD46, SNORA21, SNORD28, SNORA47, SNORD66, SNORA68, SNORA78 (snoRNAs), piR-65, piR-34871, piR-52200, piR651 (piRNAs), hY4 5′ fragments (YRNA), FAM83A-AS1, WRAP53, NKX2-1-AS1 (NAT), DUXAP8, SFTA1P (pseudogene transcript) and, Uc.454 (T-UCR), her.