Lnc-Mical3-2 Is a Colorectal Cancer-Unique Lncrna That Suppresses Tumorigenic Progression via Distinct Gene/Signaling Networks

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details


Colorectal cancer (CRC) is one of the prevalent health problems worldwide, especially in developed countries, and also represents the third leading cause of cancer-related mortality globally. In spite of the advances in CRC disease management, clinical outcomes and prognosis of CRC have not been significantly improved, implying that the underlying pathogenic mechanism remains to be further refined. Toward this end, transcriptomic perturbations have been extensively documented as an important molecular hallmark in association with the malignant state. In this context, long non-coding RNAs (lncRNAs), despite the lack of protein-coding potential, have emerged as crucial regulators in the diverse biological processes connected with tumorigenesis. To better understand the CRC oncogenesis and disease progression from the transcriptome perspective, we previously conducted deep sequencing-based expression profiling to catalogue non-coding RNA distinctions between tumor and matched normal tissues from 104 CRC patients. By further integrating with the public TCGA datasets, we uncovered a novel CRC tissue-specific and survival-associated lncRNA, termed lnc-MICAL3-2, whose tumor-suppressive role and positive prognostic value are evidenced by its down-regulation in CRC and also association with the patient overall survival and disease-free survival. The goal of this project is to dissect the functional roles and pathological significance of this CRC-unique lncRNA, particularly in relation to CRC tumorigenesis. In the first part, we will molecularly characterize the lnc-MICAL3-2 transcripts and decode the cellular outcome of lnc-MICAL3-2 mis-expression both in vitro and in vivo by respectively using cell biological and animal models. Upon establishing the involvement of this unique lncRNA in CRC carcinogenesis, our next aim is to in silico map the cellular/signaling networks regulated by lnc-MICAL3-2 and further to experimentally delineate its probably targets and functional implications. Finally, we set out to dissect mechanistically the cellular consequences mediated coordinately by lnc-MICAL3-2 and its targets in CRC and to decipher the patho-physiological relevance of these lnc-MICAL3-2 networks via in-depth analysis of different cohort datasets with clinical information. As a basis for this experimental design, our preliminary results have already revealed that lnc-MICAL3-2 may impart an isoform-dependent regulation of the TGF-β canonical and non-canonical signaling pathways. Functional link of our lncRNA to this CRC-promoting signaling will be further studied accordingly. Overall, the results derived from this proposed study will constitute novel and informative advancement in our understanding of the lnc-MICAL3-2-regulated networks underlying CRC development and may provide insights into developing new strategies for CRC management and monitoring.

Project IDs

Project ID:PC10907-0945
External Project ID:MOST109-2320-B182-013
Effective start/end date01/08/2031/07/21


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