MicroRNA-1246 promotes growth and metastasis of colorectal cancer cells involving CCNG2 reduction

Abstract

Colorectal cancer (CRC) is the third most common cancer type and the fourth leading cause of cancer‑associated mortality worldwide. MicroRNA (miR)‑1246 is involved in differentiation, invasion, metastasis and chemoresistance of certain types of tumor cells. CCNG2 encodes an unconventional cyclin homolog, cyclin G2 (CycG2), associated with growth inhibition, which correlated significantly with lymph node metastasis, clinical stage, histological grade and poor overall survival in numerous cancer types. To investigate the regulation of miR‑1246 on CycG2 expression, and their effects on proliferation and metastasis of CRC, HCT‑116 and LOVO cells were transfected with pre‑miR‑1246 anti‑miR‑1246 and their negative controls. It was demonstrated that the expression of miR‑1246 was significantly increased in CRC tissues and cell lines, which was the opposite of CycG2. miR‑1246 negatively regulated the expression of CycG2 in HCT‑116 and LOVO CRC cells. CCNG2 is a direct target of miR‑1246 in CRC cells. Overexpression of miR‑1246 induced cell proliferation, migration and invasion, while knockdown of miR‑1246 inhibited proliferation, migration and invasion in the CRC cells. Upregulation of miR‑1246 mediated the malignant progression of CRC and is partly attributed to the downregulation of the expression of CycG2. Consequently, these findings provided a molecular basis for the role of miR‑1246/CCNG2 in the progression of human CRC and suggested a novel target for the treatment of CRC.

Exosomal microRNA miR-1246 induces cell motility and invasion through the regulation of DENND2D in oral squamous cell carcinoma

“…Therefore, we excluded miR-342–3p from further investigation and continued exploring the functional mechanism of miR-1246 . Recently, extracellular miR-1246 has been reported to promote lung cancer proliferation and enhance radioresistance2728. Importantly, in our study, we found that DENND2D is a direct target of miR-1246 and demonstrated a gene expression pattern that resembled that of HOC313-LM cells (Fig.…”

“…The most salient finding was a set of 11 miRNAs that are commonly upregulated in HOC313-LM cells at the cellular and exosomal level (Table 1). Based on these results, we focused on seven miRNAs, miR-17, miR-30a-3p, miR-30a-5p, miR-92a, miR-181a, miR-342–3p and miR-1246 , all of which have been reported as oncogenic miRNAs (oncomiRs)22232425262728. Using quantitative RT-PCR (qRT-PCR), we could validate the differential expression of six of these miRNAs (all except miR-92a ) in cells and exosomes (Supplementary Fig.…”

Exosomal MicroRNA MiR-1246 Promotes Cell Proliferation, Invasion and Drug Resistance by Targeting CCNG2 in Breast Cancer

“…In addition, miR-1246 directly targets CCNG2 expression by binding to its 3′UTR. Many studies have evaluated the importance of exosomes in cancer progression [14, 15]; for instance, exosomes secreted by highly metastatic cells contribute significantly to cancer progression of poorly metastatic cells, which is consistent with the idea that cancer cells interact with each other through exosomes. We found that exosomes isolated from MDA-MB-231 cells could induce malignant features in HMLE cells by increasing their cell growth and cell invasion.…”

Lack of miR‐1246 in small extracellular vesicle blunts tumorigenesis of laryngeal carcinoma cells by regulating Cyclin G2

“…In addition, the correlation between miR‐1246 and the target gene CCNG2 still needs further study. Although the direct regulating relationship has been confirmed in oral, breast, pancreatic, and colorectal cancers we still need to clarify in LSCC.…”