Int J Biol Sci 2022; 18(9):3777-3794. doi:10.7150/ijbs.70546 This issue

Research Paper

HTR1D functions as a key target of HOXA10-AS/miR-340-3p axis to promote the malignant outcome of pancreatic cancer via PI3K-AKT signaling pathway

Wu Wu1*, Qujin Li1*, Zhu Zhu1*, Chunming Li1, Peilin Lu2, Xi Zhou3, Yujing Huang2, Yan Liu1,4✉, Menghao Wang1✉, Jianping Gong1✉

1. Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
2. Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
3. Department of Gastroenterology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
4. Department of Gastroenterology, The Fifth People's Hospital of Chengdu, Chengdu, Sichuan, China
*These authors have contributed equally to the work

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Citation:
Wu W, Li Q, Zhu Z, Li C, Lu P, Zhou X, Huang Y, Liu Y, Wang M, Gong J. HTR1D functions as a key target of HOXA10-AS/miR-340-3p axis to promote the malignant outcome of pancreatic cancer via PI3K-AKT signaling pathway. Int J Biol Sci 2022; 18(9):3777-3794. doi:10.7150/ijbs.70546. Available from https://www.ijbs.com/v18p3777.htm

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Abstract

Graphic abstract

Competing endogenous RNAs (ceRNAs) are a newly discovered class of molecular regulators involved in many diseases, especially tumors. Therefore, exploration of the potential ceRNA regulatory network regarding the occurrence and development of pancreatic cancer will provide a new theoretical basis for its diagnosis and treatment. Based on the above background, we applied a bioinformatics approach to mine the public database The Cancer Genome Atlas (TCGA) and performed a series of subsequent molecular biology assays to confirm the hypothesis that HOXA10-AS/ miR-340-3p/HTR1D axis could modulate the malignant progression of pancreatic cancer. Here, our present study demonstrated that the expression level of HTR1D, positively correlated with the level of lncRNA HOXA10-AS and negatively associated with the level of miR-340-3p, was significantly increased in pancreatic cancer cell lines (PCs) compared with that in normal HPDE6-C7 cells. Knocking down HTR1D obviously inhibited the proliferation and migration of PCs and promoted apoptosis by upregulating p-AKT. Elevated miR-340-3p blocked the progression of pancreatic cancer by downregulating HTR1D. Lessened level of lncRNA HOXA10-AS reduced the sponging of miR-340-3p, resulting in an increase of miR-340-3p and a subsequent decrease of HTR1D to ultimately suppress the malignant biological behaviors of cancer. These data illustrated that the HOXA10-AS/miR-340-3p/HTR1D ceRNA axis acted a crucial part in the malignant biological behavior of pancreatic cancer in an AKT-dependent manner.

Keywords: pancreatic cancer, ceRNA, HTR1D, HOXA10-AS, miR-340-3p