Molecular Landscape of LncRNAs in Prostate Cancer: A focus on pathways and therapeutic targets for intervention

Abstract

Background One of the most malignant tumors in men is prostate cancer that is still incurable due to its heterogenous and progressive natures. Genetic and epigenetic changes play significant roles in its development. The RNA molecules with more than 200 nucleotides in length are known as lncRNAs and these epigenetic factors do not encode protein. They regulate gene expression at transcriptional, post-transcriptional and epigenetic levels. LncRNAs play vital biological functions in cells and in pathological events, hence their expression undergoes dysregulation. Aim of review The role of epigenetic alterations in prostate cancer development are emphasized here. Therefore, lncRNAs were chosen for this purpose and their expression level and interaction with other signaling networks in prostate cancer progression were examined. Key scientific concepts of review The aberrant expression of lncRNAs in prostate cancer has been well-documented and progression rate of tumor cells are regulated via affecting STAT3, NF-κB, Wnt, PI3K/Akt and PTEN, among other molecular pathways. Furthermore, lncRNAs regulate radio-resistance and chemo-resistance features of prostate tumor cells. Overexpression of tumor-promoting lncRNAs such as HOXD-AS1 and CCAT1 can result in drug resistance. Besides, lncRNAs can induce immune evasion of prostate cancer via upregulating PD-1. Pharmacological compounds such as quercetin and curcumin have been applied for targeting lncRNAs. Furthermore, siRNA tool can reduce expression of lncRNAs thereby suppressing prostate cancer progression. Prognosis and diagnosis of prostate tumor at clinical course can be evaluated by lncRNAs. The expression level of exosomal lncRNAs such as lncRNA-p21 can be investigated in serum of prostate cancer patients as a reliable biomarker.

Mechanistic studies of MALAT1 in respiratory diseases

“…EZH2 generally acts as a tumor promoter; however, owing to its methyltransferase activity, it may also act as a tumor suppressor. Among the ncRNAs, miRNAs and lncRNAs play an important regulatory role in EZH2 signaling ( Mirzaei et al, 2022b ). Thus, investigating whether MALAT1 can influence cancer progression through its regulation of EZH2 warrants further research.…”

Association between lncRNAs in plasma exosomes and diabetic retinopathy

“…Exosomes are extracellular vesicles containing specific proteins, lipids, functional mRNA, non-coding RNA and other biologically active substances. Some studies have found that in humans, changes in the number and composition of exosomes might reflect the development and pathological status of DR. Long noncoding RNAs (lncRNAs) are non-protein-encoding transcripts longer than 200 nucleotides that plays an important role in transcriptional ( 6 ), chromatin ( 7 ), and post-transcriptional regulation ( 8 ). Especially lncRNAs localized in exosomes can be secreted and enter recipient cells, and are involved in epigenetics, cell type reprogramming and genome instability regulation ( 9 ).…”

miR-140-5p and miR-140-3p: Key Actors in Aging-Related Diseases?

“…Many studies and reviews are available reporting miRNA involvement in physiological pathways and developmental processes, as well as their deregulation under pathological conditions leading to diseases, such as cancers or genetic diseases. They also have been proposed as potential biomarkers or therapeutic targets in various pathological contexts [ 33 , 34 , 35 , 36 , 37 ].…”