A novel circ_0099999/miR-330-5p/FSCN1 ceRNA crosstalk in pancreatic cancer
Background Pancreatic cancer is a lethal malignancy in both sexes throughout the world. Circular RNAs (circRNAs) have been implicated in the development of pancreatic cancer by operating as competing endogenous RNAs (ceRNAs). Here, we explored circ_0099999-mediated ceRNA activity in regulating pancr...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2021-10-01
|
| Series: | Autoimmunity |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/08916934.2021.1963958 |
| _version_ | 1827817273798164480 |
|---|---|
| author | Yang Wang Feng Zhang Dongde Wu Qun Wang Lei Nie Jing Yu |
| author_facet | Yang Wang Feng Zhang Dongde Wu Qun Wang Lei Nie Jing Yu |
| author_sort | Yang Wang |
| collection | DOAJ |
| description | Background Pancreatic cancer is a lethal malignancy in both sexes throughout the world. Circular RNAs (circRNAs) have been implicated in the development of pancreatic cancer by operating as competing endogenous RNAs (ceRNAs). Here, we explored circ_0099999-mediated ceRNA activity in regulating pancreatic tumorigenesis. Methods Ribonuclease R (RNase R) and subcellular localization assays were utilized to characterize circ_0099999. The levels of circ_0099999, microRNA (miR)-330-5p, and fascin actin-bundling protein 1 (FSCN1) were gauged by quantitative real-time PCR (qRT-PCR) and western blot. Cell proliferation, colony formation, apoptosis, migration, and invasion were evaluated by the Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, and transwell assays, respectively. The levels of glucose consumption and lactate production were determined using the assay kits. A direct relationship between miR-330-5p and circ_0099999 or FSCN1 was validated by dual-luciferase reporter assay. Tumour xenograft assays were used to analyse the role of circ_0099999 in vivo. Results Circ_0099999 was highly up-regulated in pancreatic cancer tissues and cells. Knockdown of circ_0099999 impeded cell proliferation, migration, invasion, glycolysis, and promoted apoptosis in vitro, as well as diminished tumour growth in vivo. Circ_0099999 targeted miR-330-5p, and miR-330-5p was a downstream mediator of circ_0099999 function. FSCN1 was a direct and functional target of miR-330-5p. Furthermore, circ_0099999 operated as a ceRNA for miR-330-5p to modulate FSCN1 expression. Conclusions Our findings established a novel causal mechanism, circ_0099999/miR-330-5p/FSCN1 ceRNA crosstalk, in regulating pancreatic carcinogenesis and provided that inhibition of circ_0099999 might have therapeutic benefits in pancreatic cancer. |
| first_indexed | 2024-03-12T00:32:04Z |
| format | Article |
| id | doaj.art-3fdeca32939e48e5a5fadd6f153868a8 |
| institution | Directory Open Access Journal |
| issn | 0891-6934 1607-842X |
| language | English |
| last_indexed | 2024-03-12T00:32:04Z |
| publishDate | 2021-10-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Autoimmunity |
| spelling | doaj.art-3fdeca32939e48e5a5fadd6f153868a82023-09-15T10:12:24ZengTaylor & Francis GroupAutoimmunity0891-69341607-842X2021-10-0154747148210.1080/08916934.2021.19639581963958A novel circ_0099999/miR-330-5p/FSCN1 ceRNA crosstalk in pancreatic cancerYang Wang0Feng Zhang1Dongde Wu2Qun Wang3Lei Nie4Jing Yu5Department of Hepatobiliary and Pancreatic Surgery, Hubei Cancer HospitalDepartment of Hepatobiliary and Pancreatic Surgery, Hubei Cancer HospitalDepartment of Hepatobiliary and Pancreatic Surgery, Hubei Cancer HospitalDepartment of Hepatobiliary and Pancreatic Surgery, Hubei Cancer HospitalDepartment of Hepatobiliary and Pancreatic Surgery, Hubei Cancer HospitalDepartment of Clinical Laboratory, Hubei Cancer HospitalBackground Pancreatic cancer is a lethal malignancy in both sexes throughout the world. Circular RNAs (circRNAs) have been implicated in the development of pancreatic cancer by operating as competing endogenous RNAs (ceRNAs). Here, we explored circ_0099999-mediated ceRNA activity in regulating pancreatic tumorigenesis. Methods Ribonuclease R (RNase R) and subcellular localization assays were utilized to characterize circ_0099999. The levels of circ_0099999, microRNA (miR)-330-5p, and fascin actin-bundling protein 1 (FSCN1) were gauged by quantitative real-time PCR (qRT-PCR) and western blot. Cell proliferation, colony formation, apoptosis, migration, and invasion were evaluated by the Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, and transwell assays, respectively. The levels of glucose consumption and lactate production were determined using the assay kits. A direct relationship between miR-330-5p and circ_0099999 or FSCN1 was validated by dual-luciferase reporter assay. Tumour xenograft assays were used to analyse the role of circ_0099999 in vivo. Results Circ_0099999 was highly up-regulated in pancreatic cancer tissues and cells. Knockdown of circ_0099999 impeded cell proliferation, migration, invasion, glycolysis, and promoted apoptosis in vitro, as well as diminished tumour growth in vivo. Circ_0099999 targeted miR-330-5p, and miR-330-5p was a downstream mediator of circ_0099999 function. FSCN1 was a direct and functional target of miR-330-5p. Furthermore, circ_0099999 operated as a ceRNA for miR-330-5p to modulate FSCN1 expression. Conclusions Our findings established a novel causal mechanism, circ_0099999/miR-330-5p/FSCN1 ceRNA crosstalk, in regulating pancreatic carcinogenesis and provided that inhibition of circ_0099999 might have therapeutic benefits in pancreatic cancer.http://dx.doi.org/10.1080/08916934.2021.1963958pancreatic cancercirc_0099999mir-330-5pfscn1cerna regulation |
| spellingShingle | Yang Wang Feng Zhang Dongde Wu Qun Wang Lei Nie Jing Yu A novel circ_0099999/miR-330-5p/FSCN1 ceRNA crosstalk in pancreatic cancer Autoimmunity pancreatic cancer circ_0099999 mir-330-5p fscn1 cerna regulation |
| title | A novel circ_0099999/miR-330-5p/FSCN1 ceRNA crosstalk in pancreatic cancer |
| title_full | A novel circ_0099999/miR-330-5p/FSCN1 ceRNA crosstalk in pancreatic cancer |
| title_fullStr | A novel circ_0099999/miR-330-5p/FSCN1 ceRNA crosstalk in pancreatic cancer |
| title_full_unstemmed | A novel circ_0099999/miR-330-5p/FSCN1 ceRNA crosstalk in pancreatic cancer |
| title_short | A novel circ_0099999/miR-330-5p/FSCN1 ceRNA crosstalk in pancreatic cancer |
| title_sort | novel circ 0099999 mir 330 5p fscn1 cerna crosstalk in pancreatic cancer |
| topic | pancreatic cancer circ_0099999 mir-330-5p fscn1 cerna regulation |
| url | http://dx.doi.org/10.1080/08916934.2021.1963958 |
| work_keys_str_mv | AT yangwang anovelcirc0099999mir3305pfscn1cernacrosstalkinpancreaticcancer AT fengzhang anovelcirc0099999mir3305pfscn1cernacrosstalkinpancreaticcancer AT dongdewu anovelcirc0099999mir3305pfscn1cernacrosstalkinpancreaticcancer AT qunwang anovelcirc0099999mir3305pfscn1cernacrosstalkinpancreaticcancer AT leinie anovelcirc0099999mir3305pfscn1cernacrosstalkinpancreaticcancer AT jingyu anovelcirc0099999mir3305pfscn1cernacrosstalkinpancreaticcancer AT yangwang novelcirc0099999mir3305pfscn1cernacrosstalkinpancreaticcancer AT fengzhang novelcirc0099999mir3305pfscn1cernacrosstalkinpancreaticcancer AT dongdewu novelcirc0099999mir3305pfscn1cernacrosstalkinpancreaticcancer AT qunwang novelcirc0099999mir3305pfscn1cernacrosstalkinpancreaticcancer AT leinie novelcirc0099999mir3305pfscn1cernacrosstalkinpancreaticcancer AT jingyu novelcirc0099999mir3305pfscn1cernacrosstalkinpancreaticcancer |