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Inhibition of ALAS1 activity exerts anti-tumour effects on colorectal cancer in vitro.

Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association (2020-04-10)
Yalei Zhao, Xiaoyun Zhang, Yabin Liu, Yiping Ma, Pong Kong, Tianliang Bai, Mei Han, Binghui Li
RÉSUMÉ

Colorectal cancer (CRC) is the third most common malignant tumour worldwide and the second leading cause of cancer-related deaths. Commonly, 5'-aminolevulinic acid synthase1 (ALAS1) is the rate-limiting enzyme for haem biosynthesis. Recent studies have shown that ALAS1 is involved in a number of cellular functions and has significant effects on non-small cell lung cancer (NSCLC). However, current concepts of disease pathogenesis fail to fully explain the role of ALAS1 expression and biological functions in CRC. A total of 67 paired tumour tissues and adjacent colorectal tissues were used to detect ALAS1 levels and further analyse the correlation between ALAS1 expression levels and clinical features. Using HCT116 cell lines, we studied the impact of ALAS1 on biological function by knocking down or inhibiting ALAS1. We found an increase in the levels of ALAS1 in cancer tissues compared to adjacent colorectal tissues. The increase in ALAS1 expression was closely related to the invasion depth, N staging and tumour size of CRC patients. The proliferation and metastasis of CRC cells could be inhibited by suppressing ALAS1. The abnormal expression of ALAS1 is closely related to the proliferation and metastasis of CRC cells, suggesting that ALAS1 may be a novel therapeutic target for the treatment of CRC.

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4,6-Dioxoheptanoic acid, powder
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MISSION® esiRNA, targeting human ALAS1