Linear and Circular Long Non-Coding RNAs in Acute Lymphoblastic Leukemia: From Pathogenesis to Classification and Treatment

Abstract

The coding regions account for only a small part of the human genome, and the remaining vast majority of the regions generate large amounts of non-coding RNAs. Although non-coding RNAs do not code for any protein, they are suggested to work as either tumor suppressers or oncogenes through modulating the expression of genes and functions of proteins at transcriptional, posttranscriptional and post-translational levels. Acute Lymphoblastic Leukemia (ALL) originates from malignant transformed B/T-precursor-stage lymphoid progenitors in the bone marrow (BM). The pathogenesis of ALL is closely associated with aberrant genetic alterations that block lymphoid differentiation and drive abnormal cell proliferation as well as survival. While treatment of pediatric ALL represents a major success story in chemotherapy-based elimination of a malignancy, adult ALL remains a devastating disease with relatively poor prognosis. Thus, novel aspects in the pathogenesis and progression of ALL, especially in the adult population, need to be further explored. Accumulating evidence indicated that genetic changes alone are rarely sufficient for development of ALL. Recent advances in cytogenic and sequencing technologies revealed epigenetic alterations including that of non-coding RNAs as cooperating events in ALL etiology and progression. While the role of micro RNAs in ALL has been extensively reviewed, less attention, relatively, has been paid to other non-coding RNAs. Herein, we review the involvement of linear and circular long non-coding RNAs in the etiology, maintenance, and progression of ALL, highlighting the contribution of these non-coding RNAs in ALL classification and diagnosis, risk stratification as well as treatment.

Long non‐coding RNAs regulate treatment outcome in leukemia: What have we learnt recently?

“…About 10%–15% of the childhood and 25% of the adulthood ALL cases are derived from T‐cell progenitors, and their prognosis is poorer than those with B‐cell ALL, partly due to higher rates of chemoresistance and relapse 79 . CDKN2B‐AS1 promotes the resistance against adriamycin via the miR‐335‐3p/TRAF5 axis in pediatric T‐cell ALL 81 . The lncRNA PPM1A‐AS can regulate important signaling molecules including Notch4, STAT3, and AKT, to promote cell proliferation and inhibit cell apoptosis 80 …”

“…79 CDKN2B-AS1 promotes the resistance against adriamycin via the miR-335-3p/TRAF5 axis in pediatric T-cell ALL. 81 The lncRNA PPM1A-AS can regulate important signaling molecules including Notch4, STAT3, and AKT, to promote cell proliferation and inhibit cell apoptosis. 2.2.4 | Therapeutic resistance in chronic lymphocytic leukemia and role of lncRNAs CLL is one type of mature B-cell neoplasms and it has a non-leukemic manifestation named as small lymphocytic lymphoma.…”

Harnessing the potential of long non-coding RNAs in breast cancer: from etiology to treatment resistance and clinical applications

“…Liquid biopsy, a more accessible, cost-effective, and repeatable sampling process, serves as a valuable source for such biomarkers, avoiding tumor heterogeneity issues ( 15 ). Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts exceeding 200 nucleotides in length ( 16 ). Researchers have discovered abnormal lncRNA expression in both BC cell lines and tissues ( 17 ), revealing their potential role in breast cancer initiation and development.…”

PIWIL1 gene polymorphism and pediatric acute lymphoblastic leukemia relapse susceptibility among Chinese children: a five-center case–control study

“…Non-coding RNAs (ncRNAs) are divided into linear RNAs and circular RNAs. Based on the size and location, linear ncRNAs are classified into several types including transfer RNAs, ribosome RNAs, small nucleolar RNAs, small nuclear RNAs, microRNAs, long non-coding RNAs, and PIWI-interacting RNAs (piRNAs) (4). PiRNAs were discovered in 2006; they are single-stranded RNAs with a length of 26-31 nucleotides (5).…”