Potential Long Non-coding RNA Research Articles

Drugging the lncRNA MALAT1 via LNA gapmeR ASO inhibits gene expression of proteasome subunits and triggers anti-multiple myeloma activity

The biological role and therapeutic potential of long non-coding RNAs (lncRNAs) in multiple myeloma (MM) are still to be investigated. Here, we studied the functional significance and the druggability of the oncogenic lncRNA MALAT1 in MM. Targeting MALAT1 by novel LNA-gapmeR antisense oligonucleotide antagonized MM cell proliferation and triggered apoptosis both in vitro and in vivo in a murine xenograft model of human MM. Of note, antagonism of MALAT1 downmodulated the two major transcriptional activators of proteasome subunit genes, namely NRF1 and NRF2, and resulted in reduced trypsin, chymotrypsin and caspase-like proteasome activities and in accumulation of polyubiquitinated proteins. NRF1 and NRF2 decrease upon MALAT1 targeting was due to transcriptional activation of their negative regulator KEAP1, and resulted in reduced expression of anti-oxidant genes and increased ROS levels. In turn, NRF1 promoted MALAT1 expression thus establishing a positive feedback loop. Our findings demonstrate a crucial role of MALAT1 in the regulation of the proteasome machinery, and provide proof-of-concept that its targeting is a novel powerful option for the treatment of MM.

NORVAS – Therapeutic and Biomarker Potential of long non-coding RNAs in Vascular Disease – H2020

NORVAS – Therapeutic and Biomarker Potential of long non-coding RNAs in Vascular Disease – H2020

The Function and Therapeutic Potential of Long Non-coding RNAs in Cardiovascular Development and Disease.

The popularization of genome-wide analyses and RNA sequencing led to the discovery that a large part of the human genome, while effectively transcribed, does not encode proteins. Long non-coding RNAs have emerged as critical regulators of gene expression in both normal and disease states. Studies of long non-coding RNAs expressed in the heart, in combination with gene association studies, revealed that these molecules are regulated during cardiovascular development and disease. Some long non-coding RNAs have been functionally implicated in cardiac pathophysiology and constitute potential therapeutic targets. Here, we review the current knowledge of the function of long non-coding RNAs in the cardiovascular system, with an emphasis on cardiovascular development and biology, focusing on hypertension, coronary artery disease, myocardial infarction, ischemia, and heart failure. We discuss potential therapeutic implications and the challenges of long non-coding RNA research, with directions for future research and translational focus.

Potential of long non-coding RNAs in cancer patients: From biomarkers to therapeutic targets.

Because of high specificity and easy detection in the tissues, serum, plasma, urine and saliva, interest in exploring the potential of long non-coding RNAs (lncRNAs) in cancer patients continues to increase. LncRNAs have shown potential as a biomarker in the diagnosis and prognosis of bladder cancer, prostate cancer, gastric cancer, pancreatic cancer, breast cancer and many other cancer types. Some lncRNAs have also been used as adjunct to improve the specificity and sensitivity of existing biomarkers. The molecular tools such as RNA-seq, RNA-FISH, ic-SHAPE and quantitative real-time PCR have been used for examining the lncRNAs' potential. Some lncRNAs such as PCA3 is now routinely used in the clinic for the diagnosis of prostate cancer. Single nucleotide polymorphisms (SNPs) in lncRNAs can also be used as a predictor of cancer risk. Although ongoing studies continue to unravel the underlying mechanism, some lncRNAs have been used as therapeutic targets for the selective killing of cancer cells in patients. Thus lncRNAs are emerging as convenient and minimally invasive diagnostic/prognostic markers, and also as therapeutic target. Companies such as the Curna Inc., MiNA Therapeutics Ltd. and RaNA Therapeutics Inc. have been taking steps to develop lncRNA based strategies against cancer. In this review, we discuss the potential of lncRNAs as biomarkers and therapeutic targets in cancer patients.