Non-coding RNA, splicing regulators and RNA promoters: an insight into the molecular basis of colorectal cancer

Colorectal cancer (CRC) is considered as a significant cause of death among cancer-related mortality rates ^[1]. The guidelines promoted by different medical associations keep pushing and promoting effective screening programs, which have increased the early diagnosis of CRC and vastly improved their chances of recovery.

However, the 5-year survival rate amongst late-stage CRC patients remains low, particularly due the lack of effective therapeutic choices ^[2]. Understanding the molecular basis of the disease will shed some light on potential therapeutic targets, diminishing the odds of death and increasing their life quality.

A Regulatory Research of the Long Noncoding RNA Function on CRC

Tumorigenesis is a long and notoriously difficult process to understand. Thankfully, advancement in the next generation sequencing data services have allowed researchers to unravel this herculean task. Many oncogenic genes are simultaneously responsible for altering transcription factors (TF) and their signalling pathways.

The importance of non-coding RNA, such as long-noncoding RNAs (lncRNAs), have increased drastically, as previous studies have demonstrated a possible role in many diseases, such as different types of cancer ^{[3] [4]}. Thus, figuring out where lncRNAs are involved in the tumorigenesis of CRC and its interaction with other proteins and their TF will prove useful.

In this study^[5], researchers demonstrated the lncRNA LOC90024 is responsible for encoding a small protein, but with enormous implications. Said protein will then interact with other transcription factors, unleashing the chain of events that culminate in cancer growth.

Tumor tissue of CRC patients, noncancerous tissue of patients and parental cells lines were used. These samples were subjected to ribosome-bound RNAs purification and RNA sequencing, to identify if the LOC90024 lncRNA could, or not, bind to any ribosome. And the sequencing of these mRNA and lncRNA samples (provided by Novogene), along with other techniques, such as immunochemistry assay, were used to determine the expression of certain proteins.

The lnc-RNA LOC90024 is, in itself, not an oncogenic promoter. However, it’s capable of encoding a small protein (SRSP). This protein interacts with splicing regulators, thus, altering and disregulating their splicing capabilities, as it happens with SRSF3. Instead, SRSF3 further binds to certain transcription factors, such as Sp4. This leads to an overexpression of the carcinogenic L-Sp4 isoform.

Novogene Related Services

Novogene’s exceeding and trustworthy capabilities allow to provide professional and comprehensive sequencing technology. Non-coding RNA is gaining attention, as more and more researchers gradually uncover its possible roles in many pathologies, from neurodegenerative disorders to cancer.

Long non-coding RNA sequencing service (lncRNA-seq) is a comprehensive next-generation method to detect the transcripts with a length of over 200nt, which do not encode protein and perform as regulatory elements in multiple biological processes.

However, the progressive library preparation enables information enrichment and gene expression profiling for both coding and non-coding transcripts from a high-sensitive transcriptomic perspective. Bioinformatic analysis does not reveal the quantification and functional enrichment of the target transcripts, but also indicates the strand orientation and regulatory relation of lncRNA targeted mRNA.

RNA-seq, and other NGS technologies, will continue providing the biomedical community more tools to search for potential therapeutic targets.

References:

1. Brody H. Colorectal cancer. Nature. 2015 May 14;521(7551):S1. doi: 10.1038/521S1a. PMID: 25970450. [Nature]
2. Lim KG, Lee CS, Chin DHJ, et al. Clinical characteristics and predictors of 5-year survival among colorectal cancer patients in a tertiary hospital in Malaysia. J Gastrointest Oncol. 2020;11(2):250-259. doi:10.21037/jgo.2020.02.04 [J Gastrointest Oncol.]
3. John S. Mattick, Igor V. Makunin, Non-coding RNA, Human Molecular Genetics, Volume 15, Issue suppl_1, 15 April 2006, Pages R17–R29 [Oxford Academic]
4. Wang FW, Cao CH, Han K, Zhao YX, Cai MY, Xiang ZC, Zhang JX, Chen JW, Zhong LP, Huang Y, Zhou SF, Jin XH, Guan XY, Xu RH, Xie D. APC-activated long noncoding RNA inhibits colorectal carcinoma pathogenesis through reduction of exosome production. J Clin Invest. 2019 Feb 1;129(2):727-743. doi: 10.1172/JCI122478. Epub 2019 Jan 14. PMID: 30511962; PMCID: PMC6355227. [J Clin Invest]
5. Meng N, Chen M, Chen D, Chen XH, Wang JZ, Zhu S, He YT, Zhang XL, Lu RX, Yan GR. Small protein hidden in lncRNA LOC90024 promotes “Cancerous” RNA splicing and tumorigenesis. Advanced Science. 2020 May;7(10):1903233.[Advanced Science]