Human metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA known to be highly expressed in several tumors. In colorectal cancer (CRC), MALAT1 promotes cell proliferation, metastasis, and invasion in vitro and in vivo. This study aimed to investigate the effect of MALAT1 on the proliferation, migration, and drug sensitivity of CRC cells in vitro and in vivo and the mechanisms involved therein. We observed increased expression of MALAT1 in six CRC cell lines compared to that in normal cells, suggesting its involvement in CRC progression. Downregulation of MALAT1 inhibited cell migration and induced apoptosis in vitro and inhibited tumor growth and metastasis in nude mice. Furthermore, MALAT1 silencing downregulated the expression of ATP-binding cassette transporters (ABC), breast cancer resistance protein (BCRP), and multi-drug resistance proteins including MDR1 and MRP1, resulting in decreased resistance of cancer cells to 5-FU. In addition, the metastasis and invasion of HCT-116 and HCT-116/5-FU cells were regulated via targeting miR-20b-5p. Based on these observations, we infer that inhibition of MALAT1 suppressed CRC progression and metastasis and improved the sensitivity of cancer cells to 5-FU. The present study proposes a new direction to investigate the molecular mechanisms underlying the invasion and metastasis of CRC, whereby the interaction between MALAT1 and miR-20b-5p could be a novel therapeutic target for CRC.

中文翻译：

---

MALAT1的抑制作用可减少肿瘤的生长和转移，并提高结直肠癌的药物敏感性。

与人类转移相关的肺腺癌转录本1（MALAT1）是一种长的非编码RNA，已知在几种肿瘤中高度表达。在结直肠癌（CRC）中，MALAT1在体内外促进细胞增殖，转移和侵袭。这项研究旨在调查MALAT1在体外和体内对CRC细胞增殖，迁移和药物敏感性的影响以及其中所涉及的机制。我们观察到与正常细胞相比，六种CRC细胞系中MALAT1的表达增加，表明其参与CRC进程。MALAT1的下调抑制了裸鼠体内的细胞迁移并诱导了细胞凋亡，并抑制了肿瘤的生长和转移。此外，MALAT1沉默下调了ATP结合盒转运蛋白（ABC），乳腺癌抗性蛋白（BCRP）的表达，以及包括MDR1和MRP1在内的多药耐药蛋白，导致癌细胞对5-FU的耐药性降低。另外，通过靶向miR-20b-5p来调节HCT-116和HCT-116 / 5-FU细胞的转移和侵袭。基于这些观察，我们推断抑制MALAT1可抑制CRC的进展和转移，并提高癌细胞对5-FU的敏感性。本研究为研究CRC侵袭和转移的分子机制提出了一个新的方向，从而使MALAT1和miR-20b-5p之间的相互作用成为CRC的新型治疗靶点。基于这些观察，我们推断抑制MALAT1可抑制CRC的进展和转移，并提高癌细胞对5-FU的敏感性。本研究为研究CRC侵袭和转移的分子机制提出了一个新的方向，从而使MALAT1和miR-20b-5p之间的相互作用成为CRC的新型治疗靶点。基于这些观察，我们推断抑制MALAT1可抑制CRC的进展和转移，并提高癌细胞对5-FU的敏感性。本研究为研究CRC侵袭和转移的分子机制提出了一个新的方向，从而使MALAT1和miR-20b-5p之间的相互作用成为CRC的新型治疗靶点。