Ju Banglv, Liu Zhilan, Nai Chao, Zhu Xinyong
Department of Hepatobiliary Surgery, The Seventh Medical Center of Chinese PLA General Hospital Beijing 100700, China.
Department of Gastroenterology, Qinghai Provincial People's Hospital Xining 810007, Qinghai, China.
Am J Transl Res. 2020 Jun 15;12(6):2695-2702. eCollection 2020.
Long non-coding RNAs (LncRNAs) have been shown to be involved in diverse cellular and physiological processes. Recent studies have proved their potential as the prospective therapeutic targets for cancer treatment. Herein, we examined the role of LncRNA CASC2 in human colon cancer. The gene expression analysis showed that LncRNA CASC2 is significantly suppressed in colon cancer tissues and cell lines. The immunohistochemistry also showed considerable increase of the Ki67 in colon cancer tissues suggestive of their aggressiveness. Overexpression of CASC2 inhibited the growth of HT-29 cells. The inhibition of HT-29 growth was due to the induction of apoptosis which was accompanied by upsurge of Bax, depletion of Bcl-2 and activation of caspase-3 cleavage. Electron microscopic analysis showed CASC2 overexpression also induced autophagy in the HT-29 cells which was associated with increase in LC3B II and Beclin 1 expression. Bioinformatic approaches and dual luciferase assay showed that CASC2 controls the TRIM16 via microRNA-214 axis. TRIM16 was found to be overexpressed in all the colon cancer tissues and cell lines. Overexpression of CASC2 caused significant inhibition of TRIM16. Additionally, silencing of TRIM16 resulted in the inhibition of HT-29 cell growth similar to that of CASC2 overexpression. Taken together, CASC2 may prove to be an important therapeutic target for colon cancer treatment.
长链非编码RNA（LncRNAs）已被证明参与多种细胞和生理过程。最近的研究证实了它们作为癌症治疗潜在靶点的可能性。在此，我们研究了LncRNA CASC2在人类结肠癌中的作用。基因表达分析表明，LncRNA CASC2在结肠癌组织和细胞系中显著下调。免疫组织化学也显示结肠癌组织中Ki67显著增加，提示其侵袭性。CASC2的过表达抑制了HT-29细胞的生长。HT-29细胞生长的抑制是由于凋亡的诱导，伴随着Bax的上调、Bcl-2的消耗和caspase-3裂解的激活。电子显微镜分析表明，CASC2的过表达也诱导了HT-29细胞的自噬，这与LC3B II和Beclin 1表达的增加有关。生物信息学方法和双荧光素酶测定表明，CASC2通过微小RNA-214轴调控TRIM16。发现TRIM16在所有结肠癌组织和细胞系中均过表达。CASC2的过表达导致TRIM16的显著抑制。此外，TRIM16的沉默导致HT-29细胞生长受到抑制，类似于CASC2过表达的情况。综上所述，CASC2可能是结肠癌治疗的一个重要靶点。
