LncRNAs are central for a number of biological activities. Housekeeping ncRNAs and regulatory ncRNAs are two classes of non-coding RNAs (ncRNAs) that have restricted or no capability to code for proteins based on their biological roles.
Housekeeping ncRNAs: These ncRNA molecules are continuously made in high amounts throughout the cell. Their main job is to maintain basic cellular functions, comprise of rRNAs, tRNAs, small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs) and telomerase RNAs (P. Zhang et al., 2019) .They handle the essential functions of all cells by being expressed consistently and with little variation (Q. Chen et al., 2019).
Regulatory ncRNAs: These are the important molecules of ncRNAs. They act as central regulators, controlling gene expression at various process, including before the gene is even turned on (epigenetic), when it’s being turned on (transcriptional), and after the gene’s message is made (post-transcriptional). The main types of ncRNAs relevant to cancer include microRNA (miRNA), long non-coding RAN (lncRNA), circular RNA (circRNA), and PIWI-interacting RNA (piRNA), each of which plays major roles in cancer biology there is considerable evidence indicating that non-coding RNAs play significant roles in human cancers. They can act as tumor suppressors by activating cell death, oncogenes or prompting the initiation and progression of cancer by inhibiting the cell death pathways etc. (Yan & Bu, 2021).
MicroRNAs: MicroRNAs are small non-coding RNA molecules that are enormously conserved and have a role in regulating the different pathway and expression of different genes. RNA polymerases II and III transcribe microRNAs, generating precursors that are cleaved many times to create mature microRNA(MacFarlane & Murphy, 2010). The majority of additional miRNA genes are located in intronic regions, where they might be transcribed and included in the list of annotated genes. Nuclear RNase III Drosha crops lengthy primary transcripts (pri-miRNAs), the precursors of miRNAs, into hairpin-shaped pre-miRNAs in mammals. This cleavage event is significant because it produces the best substrate for the processes that follow and predetermines the mature miRNA sequence (Lee et al., 2004).Therefore, any misregulation of the miRNAs may cause significant cellular regulatory disruptions and could result in the development of malignant phenotypes. In fact, it has been demonstrated that many malignancies have altered miRNA profiles(Pillai, 2005) To present, around 2000 human miRNAs have been identified (Kozomara & Griffiths-Jones, 2011). Recently, it was discovered that the microRNA (miRNA)-guided RNA silencing mechanism controls gene expression. One recently identified mechanism that controls messenger RNA (mRNA)-based gene expression is the microRNA (miRNA)-guided RNA silencing pathway. When Lee et al. observed that the lin-4 transcript encoded for a small RNA of about 22 nt, which was found to contain sequences complementary to a repeated sequence element in the 3′ nontranslated region(NTR) of the lin-14 mRNAion at the messenger RNA (mRNA) level, they initially reported the phenomenon in the nematode Caenorhabditis elegans. When Lee et al. observed that the lin-4 transcript encoded for a short RNA of about 22 nt, they first reported seeing this occurrence in the nematode Caenorhabditis elegans. This result showed that RNA:RNA interaction might control the lin-14 mRNA.(Perron & Provost, 2008) miRNAs plays important role in several regulatory pathways, such as control the development, hematopoietic stem cell differentiation, apoptosis, cell proliferation, and organ development, have been uncovered by recent investigations (Bartel, 2004).
Circular RNA: This kind of non-coding RNA known as circular RNAs (circRNAs) are differentiated by their 3′ and 5′ ends are covalently bonded which form a covalently closed loop structure, leaving no free ends produced by a distinctive kind of alternative splicing known as backsplicing. CircRNAs are becoming known as a different class of molecules that regulate transcription, protein translation, and miRNA activities to alter the expression of genes (Ebbesen et al., 2017). It is significant to add that, even though the fact that circRNAs are generally thought of as a noncoding form of RNA, there is evidence to suggest that they can be translated into useful proteins. Some circRNAs are made up of exons, and some of them even have stable open-reading frames and ribosome entry sites. There is proof that a particular group of circRNAs interacts with ribosomes and contain exonic start codons in their composition(Drula et al., 2020). CircRNA have greater stability over linear RNAs, circRNAs may have diverse roles. Human circRNA CDR1as has been discovered to act as a negative regulator (or “sponge”) of the microRNA miR-7(Hansen et al., 2013). According to recent research, reverse complementary sequences in the introns aids in surrounding circularized exons in mammals facilitate the synthesis of circular RNA (Rybak-Wolf et al., 2015). Once generated, circRNAs can live in the nucleus, as in the case of multiexon-circles that have retained introns Citation9, or, like most circRNAs, they can be exported to the cytoplasm(Ebbesen et al., 2017).
Long non-coding RNA: Many of long non-coding RNAs (lncRNAs), which are RNA molecules longer than 200 nt that are not translated by ribosome into functional proteins, are formed by the extensive transcription of genomes. A huge and incredibly diversified collection of transcripts with varying genetic heritages and biogenesis are included in this all-inclusive explanation. Human GENCODE data show that the human genome has more than 16,000 lncRNA genes, while some estimates suggest the total number of human lncRNAs is over 100,000 (Statello et al., 2021a). These include lncRNAs from intergenic regions (lincRNAs), sense or antisense transcripts that overlap with other genes, and lncRNAs produced by RNA polymerase II (Pol II), among other RNA polymerases. The resulting lncRNAs are capped at their 5′ ends by 7-methyl guanosine (m7G), have polyadenylation at their 3′ ends, and are often spliced similarly to mRNAs. It is crucial to keep in mind that enhancer and promoter areas are translated into enhancer RNAs (eRNAs) and promoter upstream transcripts, respectively (Wu et al., 2017). LncRNAs are found in the cytoplasm, mitochondria, and nucleus and can be either circular or linear(Ponting et al., 2009). Certain lncRNAs are preferentially expressed in particular organs, and overall, lncRNA expression levels appear to be minor than those of protein-coding genes. On the other hand, new research indicates that unique lncRNAs could make up a sizable amount of the previously described “dark matter” of the human transcriptome (Gibb et al., 2011). The XIST lncRNA gene, which is fundamental for X-chromosome inactivation, was discovered shortly after the imprinted H19 gene, one of the first lncRNA genes ever identified (Brown et al., 1991). Long intervening/intergenic ncRNA (lincRNAs), sense lncRNAs, intronic lncRNAs, and antisense lncRNAs are the four classes into which they can be classified based on their distribution throughout the genome, comparative locations with neighboring coding genes, and transcription directions (L. Ma et al., 2013). The roles of lncRNAs can be broadly categorized as follows: functional lncRNAs, whose transcripts can control the expression of genes in cis or Trans; While lncRNAs act during transcription, their transcripts serve no purpose; absence of activities for lncRNAs that could be transcribed noises (M. B. Clark et al., 2015) lncRNAs interact with proteins, DNA, and other RNAs in cells when they are found in the cytoplasm or nucleus. They participate in the differentiation, apoptosis, and proliferation of the cell LncRNAs function in development, reproduction, aging, and disease in animals (Rinn & Chang, 2012,Batista & Chang, 2013). At several levels, lncRNAs control the expression of genes. Through their interactions with proteins, RNA, and DNA, long noncoding RNAs (lncRNAs) can influence RNA splicing, translation, stability, and neighboring and distant gene transcription, as well as chromatin structure and function. Furthermore, lncRNAs help to regulate and enhance nuclear condensates and organelles (Statello et al., 2021b). Numerous disorders, most notably malignancies, have been linked to lncRNA dysregulation. Numerous research that have shown lncRNA expression profiles linked to lung cancer have benefited from next-generation sequencing techniques(Wang et al., 2016) Differentially expressed lncRNAs have been linked to cancer due to advances in cancer transcriptome analysis and growing evidence for lncRNA function. Numerous biological processes have been linked to long noncoding RNAs (LncRNAs), and the deregulation of certain processes, including transcriptional control and genomic imprinting, is a main aspect in the development of cancer(Gibb et al., 2011).
It has been demonstrated that lncRNA expression varies throughout cancer types and that it promotes tumor development, invasion, and metastasis via a variety of mechanisms (Gupta et al., 2010).Numerous lncRNAs are known to be engaged in various pathways in a range of biological functions, including regulating the expression of the genome and inducing death, growth, and differentiation in cells(Mercer et al., 2009). Researchers have discovered a connection between certain neurological illnesses and deregulation of lncRNAs (Ng et al., 2013). Research has demonstrated that long noncoding RNAs (LncRNAs) play a role in the progression and development of lung cancer. It has also been found that the majority of LncRNAs are involved in the early stages of lung cancer. HOTAIR, H19, ANRIL, MALAT1 (lung adenocarcinoma associated transcript 1), SCAL1 (smoke and cancer-related long-chain non-coding RNA 1), lncRNA AK126698, and lncRNA GAS6-AS1 (GAS6 antisense RNA1) are just a few of the many lncRNAs linked to lung cancer (G. Xu et al., 2014).
