No abstract

Curcumin shows an anti‐cancer role in many kinds of tumors. However, the mechanism of its anti‐tumor function in esophageal squamous cell carcinoma (ESCC) remains largely unknown. Herein, we explored the therapeutic potential of curcumin for esophageal cancer. Curcumin could time‐ and dose‐dependently inhibit ESCC cells activity. Additionally, ESCC cells exposed to 20 μM of curcumin exhibited significantly decreased proliferative and invasive capacities, as well as enhanced cell apoptosis. ESCC tissues and cells exhibited significantly increased circNRIP1 expression when compared to their counterparts. circNRIP1 knockdown markedly impaired cell proliferation, clone formation, cell migration and invasion but promoted apoptosis. Exposure to 10–20 μM of curcumin inhibited circNRIP1 expression, however, overexpression of circNRIP1 could significantly restored the biological characteristics that were inhibited by curcumin exposure in vivo and in vitro. circNRIP1 promoted the malignancy of ESCC by combining miR‐532‐3p, and downstream AKT3. Curcumin inhibited AKT phosphorylation by up‐regulating miR‐532‐3p expression, thereby inhibiting the activation of the AKT pathway. In summary, curcumin is a potent inhibitor of ESCC growth, which can be achieved through the regulation of the circNRIP1/miR‐532‐3p/AKT pathway. This research may provide new mechanisms for curcumin to inhibit the malignant development of ESCC.

Colorectal cancer (CRC) is the fourth most deadly cancer worldwide, drug resistance impedes treatment of CRC. It is still urgent to find new molecular targets to improve the sensitivity of chemotherapeutic drugs. In this study, circ‐ERBB2 was upregulated in CRC cells. Upregulation of circ‐ERBB2 promoted CRC cells proliferation and clone formation, but inhibited apoptosis. We identified miR‐181a‐5p as circ‐ERBB2's target. The effect of miR‐181a‐5p on CRC cells was contrary to circ‐ERBB2, miR‐181a‐5p downregulation abolished the function of circ‐ERBB2 silencing in CRC cells. In addition, phosphatase and tensin homolog (PTEN) was verified as miR‐181a‐5p's downstream target, circ‐ERBB2 activates the Akt pathway and inhibits cell apoptosis through modulating miR‐181a‐5p/PTEN. Circ‐ERBB2 silencing significantly reduced CRC cell resistance to 5‐FU. miR‐181a‐5p downregulation abolished the role of circ‐ERBB2 knockdown in CRC cell resistance to 5‐FU. In conclusion, upregulation of circ‐ERBB2 promoted the malignancy of CRC and reduced CRC cell resistance to 5‐FU. Besides, additional mechanism study provided a novel regulatory pathways that circ‐ERBB2 knockdown promoted CRC cell sensitivity to 5‐FU by regulating miR‐181a‐5p/PTEN/Akt pathway. This research indicated that circ‐ERBB2 may be a valuable biomarker for the diagnosis and treatment of CRC.