Vol.:(0123456789) 1 3 Molecular Biology Reports https://doi.org/10.1007/s11033-020-05609-x REVIEW Emerging role of long non-coding RNAs in cancer chemoresistance: unravelling the multifaceted role and prospective therapeutic targeting Deepti Singh 1  · Mohammad Afsar Khan 1  · Hifzur R. Siddique 1 Received: 16 March 2020 / Accepted: 20 June 2020 © Springer Nature B.V. 2020 Abstract Chemotherapy is one of the important treatment modules in early as well as advanced stages of cancer. However, the major limitation of chemotherapy is the development of chemoresistance in the transformed cells of cancer patients, which leads to cancer recurrence. Long non-coding RNAs (lncRNA) are the transcripts longer than 200 nucleotides in length, which are reported to associate with the initiation, progression, recurrence, and metastasis of diferent cancers. Several lncRNAs have been implicated in the prevalence of chemoresistant phenotypes and also in the restoration of drug sensitivity in chemoresist- ant cells. LncRNAs such as HOTAIR, H19, and a lot more are involved in the chemoresistance of cancer cells. Therefore, targeting the lncRNAs may serve as a novel strategy for treating chemoresistant cancer. This review throws light on the role of lncRNA in chemoresistance along with the perspective of the therapeutic targets for the treatment of multiple cancers. Keywords LncRNA · Cancer · Chemoresistance · Signalling pathways · Therapeutic challenges Introduction In the human genome, it has been assumed that 80% of the genome has protein-coding capability. However, a larger portion of the genome is transcribed into RNA, only a small portion, i.e., < 2%, is translated into protein [1]. The transcripts which are not translated into proteins are designated as non-coding RNA (ncRNA). Based on the length of the transcript, the ncRNAs are classifed into two main classes i.e., short ncRNA (< 200 nt) and long ncRNA (> 200 nt) (Fig. 1). Earlier, the ncRNA was considered as non-functional. However, recent reports suggest that ncR- NAs play several roles such as the recruitment of regulatory molecules, regulation of protein-protein interactions, gene expressions, chromatin remodeling, chromatin interactions, and function as Natural Antisense Transcripts (NAT). Fur- thermore, the ncRNAs have been found to play a role in vari- ous physiological, developmental, and diseased conditions [1, 2]. Recently, several studies discovered the numerous important functions of ncRNAs in cancer which is among the leading causes of death worldwide. Recently, several lncRNAs are found to be involved in diferent stages of carcinogenesis [3] (Table 1). Increased expression of lncR- NAs has been observed in the tumor tissues. Initially, H19, MALAT1 (Metastasis Associated Lung Adenocarcinoma Transcript-1), and PCA3 (Prostate cancer Antigen 3) were identifed for their role in cancer [4]. Subsequently, the role of lncRNA in cancer has been identifed by the number of researchers [5]. Therefore, a detailed understanding of the aberrant expression of lncRNAs in cancer will help in the prognosis, diagnosis, and treatment of cancer. The major challenge to treat cancer patients is the devel- opment of chemoresistance because it results in cancer recurrence, distribution, and the ultimate death of the patient [6]. The molecular mechanism of chemoresistance includes higher transport pumps, mutation or suppression of tumor suppressor genes, higher epithelial to mesenchymal tran- sition (EMT), stemness of cancer cells, and mitochondrial alteration [7]. Many cross talks occur among the above aspects of chemoresistance. Recently, lncRNAs are found to be associated with chemoresistance [8]. For instance, MEG3 (maternally expressed 3) and HOTAIR (HOX tran- script antisense RNA) lncRNA are reported to contribute * Hifzur R. Siddique hifzur.zo@amu.ac.in 1 Molecular Cancer Genetics & Translational Research Lab, Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh 202002, India