Screening of MUCIN family members synergistic with MUC1 in tumor chemoresistance

doi:10.3969/j.issn.1674-8115.2022.09.015

Abstract

Abstract:

Objective ·To screen partners of mucin 1 (MUC1) in MUCIN family members that involve in chemoresistance. Methods ·Two pairs of cell lines were employed, including HeLa229/TR-CasCTL and HeLa229/TR-CasMUC1, and HeLa229/P and paclitaxel-resistant cell HeLa229/TR. Firstly, the cells were employed to detect the mRNA levels of MUCINs by quantitative real-time PCR (qPCR). The correlation of mRNA levels between MUC1 and MUCINs was analyzed. Then, Western blotting was performed to detect the protein levels of the selected MUCINs to get the proteins correlated with MUC1 at both mRNA and protein levels. IC₅₀ assay was further employed to detect the role of target protein in paclitaxel resistance by knockdown of the gene through shRNA in HeLa229/TR cells. The mean expression levels of MUC1 and MUC13 in a variety of cancer tissues were further explored in the GEPIA database. The R2 database was further employed to detect the linear correlation of the expression between MUC1 and MUC13 in cervical, colon and pancreatic cancer tissues. Finally, the expression of MUC1 and MUC13 was analyzed by the Kaplan-Meier Plotter database in relation to the survival rate of patients with gastric cancer. Results ·The detection of qPCR showed that MUC13 and MUC18 exhibited correlation with MUC1 at the mRNA level in MUCIN family members. Western blotting showed that only MUC13 protein was up-regulated with the up-regulation of MUC1, while down-regulated with the silence of MUC1. IC₅₀ assay displayed that silencing of MUC13 in HeLa229/TR decreased IC₅₀ to paclitaxel. By searching the GEPIA database, the expression levels of MUC1 and MUC13 were simultaneous high or low in a variety of cancer tissues. From the R2 database, MUC1 and MUC13 showed a positive linear correlation in cervical, colon and pancreatic cancer tissues. In addition, the negative relationship of the expression of MUC1 and MUC13 and survival rate of patients with gastric cancer from the Kaplan-Meier Plotter database was observed. Conclusion ·MUC13 is a partner for MUC1 in promoting tumor chemoresistance. The expression levels of MUC1 and MUC13 are negatively related with the survival rate of cancer patients. It's feasible for joint inhibiting MUC1 and MUC13 to overcome chemoresistance.

Key words: MUCIN family, mucin 1 (MUC1), synergistic effect, chemoresistance

CLC Number:

TANG Kairan, WU Qiong, HUANG Sijia, QIU Xudong, LI Wenyan, DENG Huayun, HUANG Lei. Screening of MUCIN family members synergistic with MUC1 in tumor chemoresistance[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(9): 1288-1295.

Figures/Tables 7

Fig 1 Detection of mRNA expressions of MUCIN family members by qPCR

Fig 2 Detection of mRNA expressions of selected MUCIN family members by qPCR

Fig 3 Protein expressions of MUC13 and MUC1

Fig 4 Downregulation of MUC13 increasing the paclitaxel sensitivity of chemoresistance tumor cells

Fig 5 Correlations between the expression levels of MUC1 and MUC13 in multiple cancer tissues by GEPIA

Fig 6 Correlation of MUC1 and MUC13 at the level of gene expression in cervical cancer, colon cancer and pancreatic cancer tissues

Fig 7 Relationships between expressions of MUC1 as well as MUC13 and survival rates of gastric cancer patients shown in Kaplan-Meier plotter database

TrendMD

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