Regulatory roles of microRNA-708 and microRNA-31 in proliferation, apoptosis and invasion of colorectal cancer cells

Abstract

MicroRNAs (miRs) function as key regulators of gene expression and their deregulation is associated with the carcinogenesis of various cancers. In the present study, the aim was to validate the potential roles and regulatory mechanisms of miR-708 and miR-31 in colorectal cancer (CRC) cells. miR-708 and miR-31 were found to be highly expressed in five CRC tissue samples. Functional studies showed that the inhibition of miR-708 and miR-31 inhibited cell proliferation and invasion, however, promoted apoptosis in vitro. Subsequently, it was identified that miR-708 and miR-31 directly target cyclin-dependent kinase inhibitor 2B (CDKN2B) by binding to the 3′ untranslated region, which suppresses the CDKN2B protein levels. In addition, the CDKN2B protein levels were significantly reduced when there was high miR-708 and miR-31 expression in the CRC tissue samples. The results indicate that miR-31 and miR-708 function in an oncogenic manner in CRC development, and inhibition of the two miRs may be used as a therapeutic strategy for patients with CRC.

Function and regulation of microRNA‐31 in development and disease

“…miR‐31 is also up‐regulated in some cancers, acting as an oncogenic miRNA (oncomiR). One well‐documented oncomiR role of miR‐31 was described in colorectal cancers (Cottonham et al, ; Cekaite et al, ; Xu et al, ; Yang et al, ; Ito et al, ; Lei et al, ; Li et al, ; Tateishi et al, ). Some of the miR‐31 targets of colon cancer include important tumor suppressors such as E2F2 (E2F Transcription Factor 2); SATB2 , RASA1 (RAS p21 GTPase activating protein 1), which was recently shown to be targeted by miR‐31 in pancreatic cancer); RHOBTB1 (Rho‐Related BTB Domain Containing 1); and TIAM1 (T Lymphoma and Metastasis Gene 1) (Cottonham et al, ; Sun et al, ; Xu et al, ; Yang et al, ; Li et al, ; Kent et al, ).…”

MicroRNA-708 is downregulated in hepatocellular carcinoma and suppresses tumor invasion and migration

“…For example, Guo et al [12] defined the 213 expression and function of miR-708, which, based on real-time PCR 214 analysis, were downregulated in glioblastoma (GBM) cells and 215 found that miR-708 might play an important role as a tumor 216 suppressor that inhibited cell proliferation and invasion and 217 induced apoptosis in the human GBM cell lines A172 and T98G; 218 Saini et al [13] defined a major tumor suppressive role for miR-708 219 in renal cancer cells, which might offer an attractive new target for 220 prognostic and therapeutic intervention. In contrast, Li et al [14] 221 revealed the elevated expression of miR-708 in high-risk common-222 acute lymphocytic leukemia (ALL) compared to standard and 223 intermediate ones; Lei et al [15] found that miR-708 might 224 function in an oncogenic manner in colorectal cancer (CRC) development, and inhibition of this miRNA might be used as a 226…”

“…and adjacent non-tumor tissues [11]. Among them, miR-708 has 53 been reported to play different roles in several types of cancers 54 [12][13][14][15]. However, little is known about the function of miR-708 in 55 human HCC.…”

“…There are various factors involved in the development of HCC, 15 including multiple viral infections, chronic inflammation, chronic 16 alcohol abuse and obesity [2]. Surgical resection and liver 17 transplantation are two promising treatment strategies for HCC, 18 however, the clinical outcome of patients remains poor, with a 19 median survival of 6-9 months following diagnosis [3].…”

Upregulation of miR-494 Inhibits Cell Growth and Invasion and Induces Cell Apoptosis by Targeting Cleft Lip and Palate Transmembrane 1-Like in Esophageal Squamous Cell Carcinoma

“…miRNAs can regulate gene expression by targeting complementary sequences primarily located on the 3 0 untranslated regions (UTRs) of target genes [11][12][13][14]. For example, microRNA (miR)-101 targets Rac1 to suppress the migration and invasion of thyroid cancer cells [15], and miR-708 and miR-31 regulate proliferation, apoptosis, and invasion of colorectal cancer cells [16]. Let-7 is downregulated in human lung cancer, and this downregulation is associated with shortened survival in these patients; however, restoration of Let-7 expression induces growth inhibition of lung cancer cells [17].…”