Up‐regulation of mir‐10b predicate advanced clinicopathological features and liver metastasis in colorectal cancer

Abstract

Given the emerging role of microRNA in tumor disease progression, we investigated the association between miRNA 10b expression, liver metastasis, and clinicopathological of colorectal cancer (CRC). Two hundred and forty‐six pairs of samples (including CRC samples and normal adjacent tissues) from CRC patients were collected from May 2004 to May 2009. All samples verified to contain at least 80% tumor cells, and were immediately frozen in liquid nitrogen and stored at −80°C or fixed in 10% formalin for paraffin embedding. The expression of miRNA‐10b in CRC tissues was evaluated using a quantitative real‐time polymerase chain reaction RT‐PCR. Correlation between miR‐10b expression and poor clinicopathological of CRC patients were analyzed using Student's t‐tests and Chi‐square tests. A Kaplan–Meier survival curve was generated following a log‐rank test. miR‐10b expression was up‐regulated in CRC tissues (P < 0.0001) and in patients diagnosed as colorectal liver metastasis (CLM) at initial involvement or during follow‐up. When the Tumor Node Metastasis (TNM) stage was taken into consideration, the expression levels of miR‐10b were positively correlated with advanced TNM stages. In addition, the miR‐10b expression of patients diagnosed as CLM at initial involvement was significantly higher than those without liver metastasis (nCLM). Similarly, those patients developed with CLM during follow‐up (FCLM) was also markedly higher than those with nCLM. miR‐10b expression was also found correlated with advanced stage (P < 0.0001), lymph node metastasis (P = 0.025), venous infiltration (P = 0.007), poorer differentiation (P = 0.002), and served as an independent prognostic factor of poor overall survival (P < 0.0001). This study demonstrated the expression of miR‐10b had strong potential to serve as a noninvasive biomarker for CRC prognosis and predicting liver metastasis.

Deregulation of CSMD1 targeted by microRNA-10b drives gastric cancer progression through the NF-κB pathway

“…Besides, the expression of microRNA-10b in patients with metastasis, including lymph node metastasis, was significantly higher than that in patients without metastasis. The up-regulation of microRNA-10b has been shown to promote the invasion and metastasis of various tumors [23][24][25][26][27][28][29]. In this study, the knockdown of miR-10b expression inhibited the growth, migration and invasion of HGC27 cells.…”

“…microRNA-10b is located in the HOX gene cluster on chromosome 2, which is closely related to tumor invasion and metastasis. Previous studies have shown that microRNA-10b is overexpressed in breast cancer [23], colorectal cancer [24], head and neck cancer [25], pancreatic cancer [26], glioblastoma [27], nasopharyngeal carcinoma [28], hepatocellular carcinoma [29] and so on. Consistent with previous reports, this study showed that the expression of microRNA-10b in GC tissues and 6 GC cell lines was higher than that in paracancerous non-tumor tissues and GES-1 cell line.…”

“…Accumulating evidence has shown that miRNAs can modulate tumor growth, metastasis, and progression by regulating multiple target genes [20][21][22]. microRNA-10b has been found to be highly expressed in many malignant tumours and related to the progress of breast cancer [23], colorectal cancer [24], head and neck cancer [25], pancreatic adenocarcinoma [26], glioblastoma [27], nasopharyngeal cancer [28], and liver cancer [29]. The pleiotropic nature of microRNA-10b was due to its suppression of multiple tumor suppressors, including ras homolog family member C (RhoC), urokinase plasminogen activator receptor (uPAR), matrix metalloproteinases (MMPs), tumor protein p53 (TP53), forkhead box O3 (FOXO3), CYLD lysine 63 deubiquitinase (CYLD), paired box 6 (PAX6), patched 1 (PTCH1), homeobox D10 (HOXD10), notch receptor 1 (NOTCH1), BCL6 transcription repressor (Bcl-6), and Kruppel like factor 4 (KLF4) [29][30][31][32][33].…”

Multi-omics Approach Reveals Distinct Differences in Left- and Right-Sided Colon Cancer

“…is tempting to believe that this result held in RCC due to the elevated expression of HOXC6. Previous studies demonstrate that the overexpression mir-10b can promote tumor invasion (31,32) and confers chemoresistance in colorectal cancer cells to 5-fluorouracil (33). In this context, 5-fluorouracil may not be suitable for the treatment of RCC due to a much higher expression level of miR-10b in RCC than LCC.…”

MicroRNA-466 (miR-466) functions as a tumor suppressor and prognostic factor in colorectal cancer (CRC)

“…miR-552 was shown to have a tumor-promoting role in CRC development by targeting Dachshund family transcription factor 1, increasing the rates of CRC cell proliferation and migration [9]. miR-10b expression was positively correlated with advanced Tumor Node Metastasis (TNM) stages, colorectal liver metastasis, lymph node metastasis, venous infiltration, poorer differentiation, and served as an independent prognostic factor of poor overall survival (OS) [10]. A recent study showed that miR-466 was underexpressed in prostate cancer (PC) and that the restoration of miR-466 expression in metastatic PC cell lines led to the impaired oncogenic functions, induced cell cycle arrest, and apoptosis in cancer cells.…”