The lncRNA XIST/miR‐125b‐2‐3p axis modulates cell proliferation and chemotherapeutic sensitivity via targeting Wee1 in colorectal cancer

Autor: Yan-Xing Chen, Huai-Qiang Ju, Zhan-Hong Chen, Jia-jia Hu, Rui-Hua Xu, Ying-Nan Wang, Jia-huan Lu, Hui Sheng, Yun Wang, Kai Yu, Pei-Shan Hu, Zexian Liu, Jia-Bo Zheng, Hai-Yu Mo, Qi-Nian Wu, Dong-dong Yang, Zhao-Lei Zeng
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
Cancer Research
Epithelial-Mesenchymal Transition
Colorectal cancer
Mice
Nude
Antineoplastic Agents
Cell Cycle Proteins
colorectal cancer
Biology
chemotherapeutic sensitivity
Real-Time Polymerase Chain Reaction
lcsh:RC254-282
Metastasis
Mice
Cell Line
Tumor
microRNA
medicine
Animals
Humans
Radiology
Nuclear Medicine and imaging
Neoplasm Metastasis
Tumor Stem Cell Assay
Aged
Cell Proliferation
Original Research
Cancer Biology
Mice
Inbred BALB C
miR‐125b‐2‐3p
drug resistance
Competing endogenous RNA
Cell growth
Middle Aged
Protein-Tyrosine Kinases
HCT116 Cells
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Long non-coding RNA
digestive system diseases
Up-Regulation
MicroRNAs
Wee1
Oncology
Drug Resistance
Neoplasm
Cancer research
biology.protein
Female
RNA
Long Noncoding
XIST
Colorectal Neoplasms
Zdroj: Cancer Medicine, Vol 10, Iss 7, Pp 2423-2441 (2021)
Cancer Medicine
ISSN: 2045-7634
Popis: Background Numerous reports on microRNAs have illustrated their role in tumor growth and metastasis. Recently, a new prognostic factor, miR‐125b‐2‐3p, has been identified for predicting chemotherapeutic sensitivity in advanced colorectal cancer (CRC). However, the specific mechanisms and biological functions of miR‐125b‐2‐3p in advanced CRC under chemotherapy have yet to be elucidated. Methods MiR‐125b‐2‐3p expression was detected by real‐time PCR (RT‐PCR) in CRC tissues. The effects of miR‐125b‐2‐3p on the growth, metastasis, and drug sensitivity of CRC cells were tested in vitro and in vivo. Based on multiple databases, the upstream competitive endogenous RNAs (ceRNAs) and the downstream genes for miR‐125b‐2‐3p were predicted by bioinformatic analysis, followed by the experiments including luciferase reporter assays, western blot assays, and so on. Results MiR‐125b‐2‐3p was significantly lowly expressed in the tissues and cell lines of CRC. Higher expression of miR‐125b‐2‐3p was associated with relatively lower proliferation rates and fewer metastases. Moreover, overexpressed miR‐125b‐2‐3p remarkably improved chemotherapeutic sensitivity of CRC in vivo and in vitro. Mechanistically, miR‐125b‐2‐3p was absorbed by long noncoding RNA (lncRNA) XIST regulating WEE1 G2 checkpoint kinase (WEE1) expression. The upregulation of miR‐125b‐2‐3p inhibited the proliferation and epithelial‐mesenchymal transition (EMT) of CRC induced by lncRNA XIST. Conclusions Lower miR‐125b‐2‐3p expression resulted in lower sensitivity of CRC to chemotherapy and was correlated with poorer survival of CRC patients. LncRNA XIST promoted CRC metastasis acting as a ceRNA for miR‐125b‐2‐3p to mediate WEE1 expression. LncRNA XIST‐miR‐125b‐2‐3p‐WEE1 axis not only regulated CRC growth and metastasis but also contributed to chemotherapeutic resistance to CRC.
Low expression of miR‐125b‐2‐3p in CRC was linked to lower chemotherapeutic sensitivity and poor survival. The lncRNA XIST promoted CRC invasion and migration by functioning as a ceRNA for miR‐125b‐2‐3p to mediate WEE1 expression. Our findings suggest that the lncRNA XIST‐miR‐125b‐2‐3p‐WEE1 axis not only regulated CRC growth and metastasis but also contributed to chemotherapeutic resistance to CRC, which may shed light on their targeted applications.
Databáze: OpenAIRE
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