Leaders in Pharmaceutical Business Intelligence (LPBI) Group

lncRNAs in Human Cancers

Curator: Larry H. Bernstein, MD, FCAP

UPDATED 9/26/2021

 

Characterizing lncRNAs in Human Cancers

Changes in long non-coding RNA expression levels are highly indicative of specific cancer types, perhaps even more so than protein-coding genes, according to a new study published today in Cancer Cell.

https://www.genomeweb.com/cancer/penn-scientists-lead-study-characterizing-lncrnas-human-cancers?

Scientists led by first authors Xiaohui Yan, Zhongyi Hu, and Yi Feng and senior authors Chi Dan and Lin Zhang, all from the University of Pennsylvania’s Perelman School of Medicine, characterized alterations in long non-coding RNAs (lncRNAs) in 5,037 tumor specimens comprising 13 cancer types from The Cancer Genome Atlas. They looked at differential changes to lncRNAs at the transcriptional, genomic, and epigenomic level to identify cancer-driving lncRNAs and predict their function.

The study found 2,316 lncRNAs altered in all 13 cancer types. As part of a more detailed analysis, the study looked at disregulation of lncRNA expression in seven cancers. Expression could be both up-regulated and down-regulated compared to normal cells, with, on average, 15 percent being up-regulated and 11 percent being down-regulated in the cancers.

UPDATED 9/26/2021

Here is some recent literature on various lncRNAs that are linked to colorectal cancer growth.

Long noncoding RNA CMPK2 promotes colorectal cancer progression by activating the FUBP3–c-Myc axis

Gao, Q., Zhou, R., Meng, Y. et al. Long noncoding RNA CMPK2 promotes colorectal cancer progression by activating the FUBP3–c-Myc axis. Oncogene 39, 3926–3938 (2020). https://doi.org/10.1038/s41388-020-1266-8

Abstract

Long noncoding RNAs (lncRNAs) have been shown to play crucial roles in cancer long noncoding RNAs (lncRNAs) have been known to play crucial roles in cancer development and progression by regulating chromatin dynamics and gene expression. However, only a few lncRNAs with annotated functions in the progression of colorectal cancer (CRC) have been identified to date. In the present study, the expression of lncCMPK2 was upregulated in CRC tissues and positively correlated with clinical stages and lymphatic metastasis. The overexpression of lncCMPK2 promoted the proliferation and cell cycle transition of CRC cells. Conversely, the silencing of lncCMPK2 restricted cell proliferation both in vitro and in vivo. lncCMPK2 was localized to the nucleus of CRC cells, bound to far upstream element binding protein 3 (FUBP3), and guided FUBP3 to the far upstream element (FUSE) of the c-Myc gene to activate transcription. lncCMPK2 also stabilized FUBP3. These results provide novel insights into the functional mechanism of lncCMPK2 in CRC progression and highlight its potential as a biomarker of advanced CRC and therapeutic target.

Long Noncoding RNA MIR17HG Promotes Colorectal Cancer Progression via miR-17-5p

Jie Xu, Qingtao Meng, Xiaobo Li, Hongbao Yang, Jin Xu, Na Gao, Hao Sun, Shenshen Wu, Giuseppe 

Familiari, Michela Relucenti, Haitao Zhu, Jiong Wu and Rui ChenDOI: 10.1158/0008-5472.CAN-18-3880 Published October 2019

Abstract

Immune dysregulation plays a vital role in colorectal cancer initiation and progression. Long noncoding RNAs (lncRNA) exhibit multiple functions including regulation of gene expression. Here, we identified an immune-related lncRNA, MIR17HG, whose expression was gradually upregulated in adjacent, adenoma, and colorectal cancer tissue. MIR17HG promoted tumorigenesis and metastasis in colorectal cancer cells both in vitro and in vivo. Mechanistically, MIR17HG increased the expression of NF-κB/RELA by competitively sponging the microRNA miR-375. In addition, RELA transcriptionally activated MIR17HG in a positive feedback loop by directly binding to its promoter region. Moreover, miR-17-5p, one of the transcribed miRNAs from MIR17HG, reduced the expression of the tumor suppressor B-cell linker (BLNK), resulting in increased migration and invasion of colorectal cancer cells. MIR17HG also upregulated PD-L1, indicating its potential role in immunotherapy. Overall, these findings demonstrate that MIR17HG plays an oncogenic role in colorectal cancer and may serve as a promising therapeutic target.

Significance: These findings provide mechanistic insight into the role of the lncRNA MIR17HG and its miRNA members in regulating colorectal cancer carcinogenesis and progression.