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Vol. 45. Issue 10.
Pages 742-752 (December 2022)
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Vol. 45. Issue 10.
Pages 742-752 (December 2022)
Original
CircRNA-001241 mediates sorafenib resistance of hepatocellular carcinoma cells by sponging miR-21-5p and regulating TIMP3 expression
CircRNA-001241 media la resistencia al sorafenib de las células de carcinoma hepatocelular mediante el esponjamiento de miR-21-5p y la regulación de la expresión de TIMP3
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Qinglong Yanga, Gang Wub,
Corresponding author
duashuai@qq.com

Corresponding author.
a Department of General Surgery, Guizhou Provincial People's Hospital, Guizhou 550000, China
b Department of General Surgery, Qinghai Provincial People's Hospital, Qinghai 810000, China
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Abstract

Hepatocellular carcinoma (HCC) is one of the major malignancies worldwide and its incidence is on the rise, closely related to advanced liver disease. Sorafenib chemotherapy is one of the main treatment options for patients with advanced HCC. Despite several reports on HCC multidrug resistance, the underlying regulatory mechanisms are still unclear. In this study, we found circ-001241 was significantly upregulated in HCC tissues and cells. Knockdown of circ-001241 markedly inhibited HCC cell proliferation and decreased sorafenib-resistance. More importantly, circRNA acts as a ceRNA to suppress the expression and activity of miR-21-5p, leading to the increase in TIMP3 expression. In addition, circRNA-001241 facilitated HCC sorafenib-resistance by regulating the miR-21-5p/TIMP3 axis. Taken together, our study elucidated the oncogenic role of circ-001241 in mediating sorafenib resistance in HCC, providing insights and opportunities to overcome sorafenib resistance in patients with advanced hepatocellular carcinoma.

Keywords:
circ-001241
Sorafenib-resistance
miR-21-5p
TIMP3
HCC
Resumen

El carcinoma hepatocelular (CHC) es una de las principales enfermedades malignas en todo el mundo y su incidencia va en aumento, estrechamente relacionada con la enfermedad hepática avanzada. La quimioterapia con sorafenib es una de las principales opciones de tratamiento para los pacientes con CHC avanzado. A pesar de varios informes sobre la multirresistencia del CHC, los mecanismos reguladores subyacentes aún no están claros. En este estudio encontramos que circ-001241 estaba significativamente regulado en los tejidos y células del CHC. El knockdown de circ-001241 inhibió notablemente la proliferación de las células del CHC y disminuyó la resistencia al sorafenib. Más importante aún, el circRNA actúa como un ceRNA para suprimir la expresión y la actividad de miR-21-5p, lo que conduce al aumento de la expresión de TIMP3. Además, circRNA-001241 facilitó la resistencia a sorafenib del CHC, mediante la regulación del eje miR-21-5p/TIMP3.En conjunto, nuestro estudio dilucidó el papel oncogénico de circ-001241 en la mediación de la resistencia a sorafenib en el CHC, proporcionando conocimientos y oportunidades para superar la resistencia a sorafenib en pacientes con carcinoma hepatocelular avanzado.

Palabras clave:
cCirc-001241
Resistencia a sorafenib
miR-21-5p
TIMP3
CHC

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