S N Nasir1, N Abu2, N S Ab Mutalib1, M Ishak1, I Sagap3, L Mazlan3, I M Rose4, R Jamal5. 1. UKM Medical Molecular Biology Institute (UMBI), UKM Medical Center, Universiti Kebangsaan Malaysia, Jalan Yaacob Latiff, Cheras, 56000, Kuala Lumpur, Malaysia. 2. UKM Medical Molecular Biology Institute (UMBI), UKM Medical Center, Universiti Kebangsaan Malaysia, Jalan Yaacob Latiff, Cheras, 56000, Kuala Lumpur, Malaysia. nadiah.abu@ppukm.ukm.edu.my. 3. Department of Surgery, Faculty of Medicine, UKM Medical Center, Universiti Kebangsaan Malaysia, Jalan Yaacob Latiff, Cheras, 56000, Kuala Lumpur, Malaysia. 4. Department of Pathology, Faculty of Medicine, UKM Medical Center, Universiti Kebangsaan Malaysia, Jalan Yaacob Latiff Cheras, 56000, Kuala Lumpur, Malaysia. 5. UKM Medical Molecular Biology Institute (UMBI), UKM Medical Center, Universiti Kebangsaan Malaysia, Jalan Yaacob Latiff, Cheras, 56000, Kuala Lumpur, Malaysia. rahmanj@ppukm.ukm.edu.my.
Abstract
PURPOSE: Colorectal cancer (CRC) is one of the most widely diagnosed cancers in men and women worldwide. With the advancement of next-generation sequencing technologies, many studies have highlighted the involvement of long non-coding RNAs (lncRNAs) in cancer development. Growing evidence demonstrates that lncRNAs play crucial roles in regulating gene and protein expression and are involved in various cancers, including CRC. The field of lncRNAs is still relatively new and a lot of novel lncRNAs have been discovered, but their functional roles are yet to be elucidated. This study aims to characterize the expression and functional roles of a novel lncRNA in CRC. METHOD: Several methods were employed to assess the function of LOC285629 such as gene silencing, qPCR, proliferation assay, BrdU assay, transwell migration assay, ELISA and protein profiler. RESULTS: Via in silico analyses, we identified significant downregulation of LOC285629, a novel lncRNA, across CRC stages. LOC285629 expression was significantly downregulated in advanced stages (Stage III and IV) compared to Stage I (Kruskal-Wallis Test; p = 0.0093). Further in-house validation showed that the expression of LOC285629 was upregulated in colorectal cancer tissues and cell lines compared to the normal counterparts, but was downregulated in advanced stages. By targeting LOC285629, the viability, proliferative abilities, invasiveness and resistance of colorectal cancer cells towards 5-fluorouracil were reduced. It was also discovered that LOC285629 may regulate cancer progression by targeting several different proteins, namely survivin, BCL-xL, progranulin, PDGF-AA, enolase 2 and p70S6 K. CONCLUSION: Our findings suggest that LOC285629 may be further developed as a potential therapeutic target for CRC treatment.
PURPOSE:Colorectal cancer (CRC) is one of the most widely diagnosed cancers in men and women worldwide. With the advancement of next-generation sequencing technologies, many studies have highlighted the involvement of long non-coding RNAs (lncRNAs) in cancer development. Growing evidence demonstrates that lncRNAs play crucial roles in regulating gene and protein expression and are involved in various cancers, including CRC. The field of lncRNAs is still relatively new and a lot of novel lncRNAs have been discovered, but their functional roles are yet to be elucidated. This study aims to characterize the expression and functional roles of a novel lncRNA in CRC. METHOD: Several methods were employed to assess the function of LOC285629 such as gene silencing, qPCR, proliferation assay, BrdU assay, transwell migration assay, ELISA and protein profiler. RESULTS: Via in silico analyses, we identified significant downregulation of LOC285629, a novel lncRNA, across CRC stages. LOC285629 expression was significantly downregulated in advanced stages (Stage III and IV) compared to Stage I (Kruskal-Wallis Test; p = 0.0093). Further in-house validation showed that the expression of LOC285629 was upregulated in colorectal cancer tissues and cell lines compared to the normal counterparts, but was downregulated in advanced stages. By targeting LOC285629, the viability, proliferative abilities, invasiveness and resistance of colorectal cancer cells towards 5-fluorouracil were reduced. It was also discovered that LOC285629 may regulate cancer progression by targeting several different proteins, namely survivin, BCL-xL, progranulin, PDGF-AA, enolase 2 and p70S6 K. CONCLUSION: Our findings suggest that LOC285629 may be further developed as a potential therapeutic target for CRC treatment.
Entities:
Keywords:
Colon cancer; In silico analysis; Long non-coding RNA; Motility; Proliferation