LncRNA CHRF: molecular mechanisms and therapeutic potentials in cardiovascular diseases, cancers and fibrosis

Abstract

Long non-coding RNAs (LncRNA), exceeding 200 nucleotides in size, have emerged as important regulators of genes involved in multiple biological functions including cell growth, migration, invasion, drug resistance and apoptosis. They are increasingly being explored in human diseases. Notably, the recently identified LncRNA Cardiac hypertrophy-related factor (CHRF) has gained attention for its involvement in the molecular mechanisms of various diseases. CHRF was originally identified as a contributive LncRNA in cardiovascular diseases. Subsequent studies also revealed that it exerts an important role in promoting fibrosis and drug resistance. However, CHRF exhibits oncogenic functions in numerous cancers, including Non-small cell lung cancer (NSCLC), Colorectal cancer (CRC), Ovarian cancer (OC), Gastric cancer (GC), indicating its crucial roles in cancer progression. CHRF exhibits tremendous potential as both therapeutic target and diagnostic biomarker, particularly in cardiomyopathy, fibrosis, and cancer. To enhance our comprehensive understanding, this review synthesizes the pathophysiological mechanisms associated with CHRF and discusses its biological significance and clinical implication. Additionally, This review provides a comprehensive discussion on therapeutic strategies based on Non-coding RNA targets and discuss the potential of targeting CHRF, which is expected to offer readers a research approach for identifying the correct target strategies.

Keywords: cancer; cardiovascular diseases; fibrosis; long non-coding RNA CHRF; molecular mechanism; target strategies.

FIGURE 1

The mechanism of LncRNA CHRF in Cardiovascular diseases.

FIGURE 2

The oncogenic CHRF’s molecular mechanisms and biological roles in cancers.

FIGURE 3

LncRNA CHRF promotes pulmonary fibrosis.

FIGURE 4

LncRNA CHRF mediated regulatory mechanisms and biological process in diseases.

FIGURE 5

Prevalent targeted strategies of Non-coding RNA. (a) siRNA: siRNA specifically binds to and degrades the corresponding ncRNA, thereby preventing the continued translation of mRNA. (b) ASO: Forming a complementary strand with a specific ncRNA sequence, an heteroduplex is created, which is then recognized and degraded by endogenous cellular RNase H, thereby inducing gene silencing. (c) CRISPR/Cas9: Utilizing site-specific Cas nucleases to induce double-strand breaks (DSBs) at specific genomic loci, which are subsequently repaired via the cell’s intrinsic non-homologous end joining (NHEJ) or homologous recombination repair (HDR) pathways, ultimately enables precise genomic modifications, including gene knockout and base editing.

FIGURE 6

The process of designing small molecule inhibitors of Non-coding RNA. (a) Defining RNA structures for small-molecule targeting (b). How to identify chemical matter that binds ncRNA: Including five methods (ALIS, Fluorescence-based assays, Microarray-based screening, Fragment mapping, DNA-encoded chemical library) (c). How to design chemical matter that binds ncRNA: There are two prevalent strategies- infoma mining and structure-based design (d). Target validation for small molecules that target ncRNA: mutation, crossing-linking, ASO-bind-Map, ncRNA degrader.