Long noncoding RNA MALAT1 mediates stem cell‐like properties in human colorectal cancer cells by regulating miR‐20b‐5p/Oct4 axis

Abstract

Cancer stem cells (CSCs) are crucial components of the tumor microenvironment that take part in tumor initiation, progression, recurrence, metastasis, and resistance to chemotherapy. This study explores the mechanisms through which CSCs maintain their stemness, especially in tumors of colorectal cancer (CRC), which thus far remain uncertain. Our findings indicated that the expression of miR-20b-5p is negatively correlated with that of metastasis-associated lung adenocarcinoma transcript-1 (MALAT1, r = −0.928, p = 0.023) and Oct4 (r = −0.894, p = 0.041) in CRC cells. We hypothesized that there may be some targeted regulatory relationships among MALAT1, miR-20b-5p, and Oct4. We proceeded to show that both si-MALAT1 and miR-20b-5p-mimic attenuated microsphere formation and self-renewal capacity, decreased the proportion of CSCs, and downregulated the expression of proteins associated with tumor cell stemness maintenance (Oct4, Nanog, sex-determining region Y-box 2, and Notch1) and cellular metabolism (glucose transporter 1, lactate dehydrogenase B, hexokinase 2, and pyruvate kinase isozyme M2) in HCT-116 cells in vitro. In addition, a xenograft model based on Balb/c mice demonstrated that the administration of either si-MALAT1 or miR-20b-5p-mimic suppressed the tumorigenicity of HCT-116 cells in vivo. The underlying mechanisms may involve the targeting of the tumor cell stemness maintenance-related factor Oct4 by miR-20b-5p. For the first time, we present the possible underlying effects of MALAT1 in influencing the stem cell-like properties of CRC cells. We propose that microRNAs and long noncoding RNAs have vital functions in mediating tumor stemness, which remain to be fully elucidated. K E Y W O R D S cancer stem cells, colorectal cancer, MALAT1, miR-20b-5p/Oct4 axis, stemness

Retracted: Long noncoding RNA MALAT1 promotes the stemness of esophageal squamous cell carcinoma by enhancing YAP transcriptional activity

“…Although the impellent roles of MALAT1 in regulating tumor stemness have been disclosed in colorectal cancer [27] and gastric cancer cells [28], to the best of our knowledge, we are the first to demonstrate the novel MALAT1-YAP axis in regulating the stemness of ESCC cells. Although the impellent roles of MALAT1 in regulating tumor stemness have been disclosed in colorectal cancer [27] and gastric cancer cells [28], to the best of our knowledge, we are the first to demonstrate the novel MALAT1-YAP axis in regulating the stemness of ESCC cells.…”

<p>LncRNA ASB16-AS1 Promotes Growth And Invasion Of Hepatocellular Carcinoma Through Regulating miR-1827/FZD4 Axis And Activating Wnt/β-Catenin Pathway</p>

“…24 LncRNA MALAT1 regulates stemness of colorectal cancer cells by interacting with miR-20b-5p to promote Oct4 expression. 25 In addition, lncRNA DGCR5 inhibits HCC cell proliferation and invasion via sponging miR-346 and activating KLF14. 26 However, how ASB16-AS1 exerts roles remains unclear.…”

The competitive endogenous RNA regulatory network reveals potential prognostic biomarkers for overall survival in hepatocellular carcinoma

“…MicroRNA‐17‐5p can exert an antitumor immune response by inhibiting dendritic cells . MicroRNA‐20b‐5p‐mimic can inhibit tumorigenicity of HCT‐116 cells in Balb/c mice . The miR‐217/MAPK1 axis is related with migration and proliferation of HCC cells .…”