Wang Jui-Ho, Lu Tzung-Ju, Kung Mei-Lang, Yang Yi-Fang, Yeh Chung-Yu, Tu Ya-Ting, Chen Wei-Shone, Tsai Kuo-Wang
Division of Colorectal Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan.
Division of Colon and Rectal Surgery, Department of Surgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23124, Taiwan.
Cancers (Basel). 2020 Oct 28;12(11):3171. doi: 10.3390/cancers12113171.
Colorectal carcinoma (CRC) is one of the most prevalent cancers worldwide and has a high mortality rate. Long noncoding RNAs (lncRNAs) have been noted to play critical roles in cell growth; cell apoptosis; and metastasis in CRC. This study determined that LOC441461 expression was significantly higher in CRC tissues than in adjacent normal mucosa. Pathway enrichment analysis of LOC441461-coexpressed genes revealed that LOC441461 was involved in biological functions related to cancer cell growth and motility. Knockdown of the LOC441461 expression significantly suppressed colon cancer cell growth by impairing cell cycle progression and inducing cell apoptosis. Furthermore, significantly higher LOC441461 expression was discovered in primary colon tumors and metastatic liver tumors than in the corresponding normal mucosa, and LOC441461 knockdown was noted to suppress colon cancer cell motility. Knockdown of LOC441461 expression suppressed the phosphorylation of MLC and LIMK1 through the inhibition of RhoA/ROCK signaling. Overall, LOC441461 was discovered to play an oncogenic role in CRC cell growth and motility through RhoA/ROCK signaling. Our findings provide new insights into the regulation of lncRNAs and their application in the treatment of colon cancer.
结直肠癌（CRC）是全球最常见的癌症之一，死亡率很高。长链非编码RNA（lncRNAs）已被发现参与CRC中的细胞生长、细胞凋亡和转移过程。本研究发现，LOC441461在CRC组织中的表达显著高于相邻正常黏膜组织。对LOC441461共表达基因的通路富集分析表明，LOC441461参与了与癌细胞生长和运动相关的生物学功能。敲低LOC441461的表达通过损害细胞周期进程和诱导细胞凋亡，显著抑制了结肠癌细胞的生长。此外，在原发性结肠肿瘤和转移性肝肿瘤中发现LOC441461的表达显著高于相应的正常黏膜组织，并且敲低LOC441461可抑制结肠癌细胞的运动。敲低LOC441461的表达通过抑制RhoA/ROCK信号通路，抑制了MLC和LIMK1的磷酸化。总体而言，发现LOC441461通过RhoA/ROCK信号通路在CRC细胞生长和运动中发挥致癌作用。我们的研究结果为lncRNAs的调控及其在结肠癌治疗中的应用提供了新的见解。
