Transforming growth factor (TGF)-β/Smad signaling plays an important role in colon cancer development, progression and metastasis. In this study we demonstrated that the microRNA-130a/301a/454 family is up-regulated in colon cancer tissues compared to paired adjacent normal mucosa, which share the same 3′-untranslational region (3′-UTR) binding seed sequence and are predicated to target Smad4. In colorectal cancer HCT116 and SW480 cells, overexpression of miRNA-130a/301a/454 mimics enhances cell proliferation and migration, while inhibitors of these miRNAs affect cell survival. The biological function of miRNA-130a/301a/454 on colon cancer cells is likely mediated by suppression of Smad4, and the up-regulation of the miRNAs is correlated with Smad4 down-regulation in human colon cancers. Collectively, these results suggest that miRNA-130a/301a/454 are novel oncogenic miRNAs contributing to colon tumorigenesis by regulating TGF-β/Smad signaling, which may have potential application in cancer therapy.

MicroRNAs have been suggested to play a vital role in regulate tumor progression and invasion. However, the expression of miR-335 in colorectal cancer (CRC) and its clinical significance are not known. Here, we report that miR-335 is a tumor suppressor by regulating expression of ZEB2. In this study, we showed that downregulated miR-335 levels in highly invasive CRC cell lines and tissues. Kaplan-Meier survival analysis indicated that patients with reduced miR-335 had a poor overall survival. Furthermore, enhancing the expression of miR-335 inhibited CRC cell migration and invasion in vitro and lung and liver metastasis in vivo, while silencing its expression resulted in increased migration and invasion. Additionally, we identified a novel miR-335 target, ZEB2, and the direct interaction between them was verified by 3'-untranslated region dual-luciferase reporter assay. In conclusion, our results demonstrate that miR-335 functions as a tumor suppressor and play a role in inhibiting metastasis of CRC cells through targeting ZEB2. These findings suggest that miR-335 may be useful as a new potential therapeutic target for CRC.

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In addition to being safe and technically feasible, LAG for locally AGC could also yield acceptable short-term oncologic outcomes.

Hepatocellular carcinoma (HCC) is a common liver malignancy worldwide accompanying with the high rate of recurrence. Accumulating reports have documented the significance of circular RNAs (circRNAs) in carcinogenesis and development of HCC. This study aimed to establish the mechanism underlying circ‐HOMER1 involvement in HCC. To this end, we identified a binding site for miR‐1322 via bioinformatics, quantitative reverse transcriptase‐polymerase chain reaction (qRT‐PCR), and dual‐luciferase reporter assays providing evidence of a direct link between circ‐HOMER1 and miR‐1322. Similarly, the target gene of miR‐1322 was investigated. Moreover, we determined the specific function of circ‐HOMER1 in HCC with the aid of qRT‐PCR based on patient clinical records, Cell Counting Kit‐8, acridine orange/ethidium bromide double fluorescence staining, flow cytometry, and wound‐healing and transwell assays. Notably, circ‐HOMER1 was upregulated in both HCC cells and tissues. This aberrant expression pattern was closely correlated with larger tumor size, higher tumor‐node‐metastasis stage, and poorer prognosis for the patients with HCC. Moreover, silenced circ‐HOMER1 inhibited cell proliferation, migration, and invasion concomitant with the promotion of apoptosis in HCC cells, and vice versa. Mechanistically, circ‐HOMER1 enhanced the inhibition of miR‐1322 on CXCL6 in HCC. Furthermore, we found that circ‐HOMER1 promoted HCC cell growth and aggressiveness by miR‐1322/CXCL6 axis. This study may provide a potential prognostic indicator and therapeutic target for patients with HCC.