Long noncoding RNA FEZF1-AS1 predicts poor prognosis and modulates pancreatic cancer cell proliferation and invasion through miR-142/HIF-1α and miR-133a/EGFR upon hypoxia/normoxia |
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Authors: | Zheng-Lin Ou Min Zhang Lian-Dong Ji Zhen Luo Tong Han Ye-Bin Lu Yi-Xiong Li |
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Institution: | 1. Department of General Surgery, Xiangya Hospital, Central South University, Changsha, People's Republic of China;2. Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China;3. Department of General Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China;4. Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China |
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Abstract: | Nowadays, pancreatic cancer (PC) remains the most lethal tumor, partially due to the invasive and treatment-resistant phenotype induced by the extent of hypoxic stress within the tumor tissue. According to previous studies, miR-142/HIF-1α and miR-133a/EGFR could modulate PC cell proliferation under hypoxic and normoxic conditions, respectively. In the present study, FEZF1-AS1, a recently described oncogenic long noncoding RNA, was predicted to target both miR-142 and miR-133a; thus, we hypothesized that FEZF1-AS1 might affect PC cell proliferation through these two axes under hypoxic or normoxic conditions. In PC cell lines, FEZF1-AS1 acted as an oncogene via promoting PC cell proliferation and invasion through miR-142/HIF-1α axis under hypoxic condition; however, FEZF1-AS1 failed to affect the protein levels of HIF-1α and VEGF under the normoxic condition, suggesting the existence of another signaling pathway under normoxic condition. As predicted by an online tool, FEZF1-AS1 could target miR-133a to inhibit its expression; under the normoxic condition, FEZF1-AS1 exerted its effect on PC cell lines through miR-133a/EGFR axis. Taken together, FEZF1-AS1 might be a promising target in controlling the aberrant proliferation and invasion of PC cell lines. |
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Keywords: | FEZF1-AS1 invasion miR-133a/EGFR miR-142/HIF-1α pancreatic cancer |
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