مقالات پذیرفته شده در هشتمین کنگره بین المللی زیست پزشکی
LncRNA and colorectal cancer
LncRNA and colorectal cancer
Keristin Hovsepian,1,*
1. Islamic Azad University: Science and Reasearch Branch
Introduction: Colorectal cancer (CRC) is one of the most common cancers. The initiation and progression of this cancer is mainly associated with the aberrant expression of various coding and non-coding genes as well as multiple risk factors such as smoking, adenomas, physical inactivity, obesity, male gender and older age. Importantly, new advances in whole genome sequencing technologies in cells have shown that over 90% of the human genome is actively transcribed. However, only 2% of transcripts are responsible for producing proteins, with the majority of the transcribed genome being non-coding RNAs (ncRNAs). Long non-coding RNAs (lncRNAs) are a subset of ncRNAs that contain over 200 nucleotides which are involved in modulating gene stability and expression. lnRNAs based on their proximity to protein encoding genes and the genomic location, can be classified as intronic lncRNAs, which indicate that they are located within the introns of protein-coding genes and have a 5' cap, but not a polyadenylation site which shows that they do not undergo the usual polyadenylation process but rather they are transcribed by RNA polymerase II. Another type of lncRNAs are intergenic lncRNAs, which are found between protein-coding genes; an example of this type of lncRNA is ELENA1. Another type to include are bidirectional lncRNAs, for example HOTTIP, as well as antisense lncRNAs, such as ST3Gal6-AS1 which are transcribed from the opposite strand of a gene and processed by one of two gene structures, ST3Gal6-AS1 in particular is transcribed from the promoter region of the ST3Gal6 gene, but in an opposite direction to the primary transcription of ST3Gal6 gene. While both the lncRNA ST3Gal6-AS1 and the ST3Gal6 gene itself are down-regulated in CRC. In addition, lncRNAs have important functions in various biological processes including cell division and differentiation, endocytosis, and transmission of neurotransmitters. Besides their role in various biological processes, lncRNAs have gained significant attention because of their oncogenic roles. LncRNAs can promote metastasis and tumor growth by regulating the expression of genes (including epigenetic, transcriptional, and post-transcriptional levels) involved in apoptosis, differentiation and cell division. Therefore, lncRNAs have potential clinical relevance and are now recognized as valuable candidates for cancer biomarkers. They hold promise in early cancer diagnosis, prognosis, and therapeutic targets for cancer patients. For example, the lncRNA PCA3 may serve as a prognostic marker for CRC, with higher levels of expression indicating poorer prognosis. Moreover, lncRNAs can be utilized in cancer immunotherapy as a system of delivery therapeutic molecules to cancer cells.
Methods: Text based on the contents found in the following journals:
A Cancer Journal for Clinicians, Carcinogenesis, British journal of cancer, Reports of Practical Oncology and Radiotherapy, Biomedicine & Pharmacotherapy, Pathology-Research and Practice, Journal of Hematology & Oncology, Phytotherapy Research, Drug Discovery Today, Journal of Hepatocellular Carcinoma, Archives of Advances in Biosciences, European Journal of Pharmacology, Journal of immunology research, Molecules, International Medical Journal of Experimental and Clinical Research, Current Molecular Medicine, Oncotarget, RNA BIOLOGY, Medicine, The International journal of biological markers, International journal of clinical and experimental pathology, Cancer medicine, Current medicinal chemistry, Clinical Chemistry and Laboratory Medicine, Cell death & disease , BMC cancer, Oncology letters, Cell proliferation, Journal of cellular and molecular medicine, Journal of cellular physiology, Molecular cancer, Non-coding RNA Research, Molecular cancer therapeutics, The Journal of Clinical Investigation, Frontiers in Cell and Developmental Biology, Cancer Cell International, BMC genomics, Trends in genetics
Results: Different types of lncRNAs, their expression levels, and their influence on signaling pathways such as Wnt/β-catenin and PI3K/Akt pathways can all contribute to varying outcomes in cancer initiation and progression. The diverse expression levels of lncRNAs in CRC can significantly affect oncogenic results. While many lncRNAs impact CRC from various aspects, some key types play a crucial role in its onset and progression. For instance, Overexpression of MALAT1 lncRNA in CRC cells has been demonstrated to enhance tumor growth through the activation of the Wnt signaling pathway. LncRNA HOTAIR, is significantly upregulated in CRC tissues and cells. Its overexpression promotes tumor growth, invasion and metastasis through silencing tumor suppressor genes including EZH2 by activating AKT/mTOR signaling pathway, further contributing to the progression of CRC. Some types of lncRNAs can have tumor suppressive roles in CRC. Such as, lncRNA MEG3 which sponges miR-103a-3p and suppresses CRC by inducing Endoplasmic reticulum (ER) stress, inhibiting cell invasion and proliferation through the upregulation of pyruvate dehydrogenase E1 subunit beta (PDHB). Also, lncRNA ANCR is found to be downregulated in CRC tissues and cells. It specifically binds to EZH2, leading to the suppression of cancer progression.
Given the significant role of lncRNAs in cancer biology, it is rational to identify suitable lncRNAs as main targets for the development of new anti-cancer drugs.
Conclusion: Increasing evidence shows that lncRNAs are important regulators that are involved in the primary characteristics of CRC through various molecular mechanisms. This indicates that they may serve as viable candidates for diagnostic and prognostic biomarkers in patients with CRC. Looking into the future, the therapeutic possibilities linked with lncRNA-based therapies can provide a significant healthcare option.