Available online 3 May 2024, 155337

Author links open overlay panel, , , , , , , , , AbstractBackground

Inappropriate expressions of various miRNAs have reported in different human malignancies. Evidence suggested that miR-330 may play as both onco-miR and/or tumor suppressor-miR in different cancers. In the present study, we evaluated effects of miR-330 on proliferation and migration of pancreatic cancer (PC) cells as well as underlying molecular mechanisms.

Design

The expression of miR-330 was evaluated in clinical tissue samples of patients with PC. Transfection of the PC cells (PANC-1) by miR-330 was conducted by pCMV vector. The cancer-related genes expression was investigated in mRNA and protein level following transfection of the PC cells. Furthermore, the PC cells viability, invasion, migration, mitochondrial membrane potential, apoptosis, autophagy, and cell cycle profile were investigated after transfection by miR-330.

Results

The results indicated that expression of miR-330 downregulated in patients with PC. Stable increase of miR‐330 expression after transfection in PC cells reduces viability, mitochondrial membrane potential, invasion, and migration. Further assessments demonstrated that upregulation of miR‐330 increases apoptosis and autophagy percentage in the PC cells. Moreover, a cell cycle arrest was observed in G1, Sub-G1, and S phases following transfection of the PC cells. These findings can be explained by modified mRNA and protein expression of apoptosis- and metastasis-related genes.

Conclusion

Our study suggested that miR-330 acts as a tumor suppressor in PC cells, and revealed that upregulation of miR-330 may provide an effective therapeutic approach for overcoming progression and metastasis in patients with PC.

Section snippetsBackground

Pancreatic cancer (PC) is a most common and invasive malignancy that responsible of cancer mortality in the world [1]. The limited early diagnosis and therapeutic methods cause to low survival rate of patients. Furthermore, insufficient knowledge on molecular mechanisms of PC is one of the important obstacles to development of prognostic, diagnostic, and therapeutic strategies [2]. So far, different molecular factors have been identified for clinical outcomes of PC, however, are not reliable

Bioinformatics analysis

In order to assessment of miR-330 expression and survival rate, miRNA data and clinical data were downloaded from The Cancer Genome Atlas (TCGA) in different cohort studies. In addition, Oncomine Cancer Microarray database was used to investigate miR-330 expression in PC cells. Numerous human expression arrays were obtained from the Gene Expression Omnibus (GEO) database. The results were presented as log2 and median centered per array, and expression levels were compared by Mann-Whitney U

Post-transfection expression of miR-330

After transfection of miR-330 to PANC-1 cancer cells, percentage of the vector‐positive cells were investigated by flow cytometry and fluorescence microscopy. The results indicated that 68.6% of the PC cells were positive for the pCMV‐miR-330 construct (Fig. 1A, B). In addition, efficiency of transfection and expression of miR-330 was investigated by quantitative RT‐PCR analysis. The results demonstrated a significant increase in expression of miR-330 in the PC cells (Fig. 1C).

Expression of cancer-related genes

Following

Discussion

Expression of miRNAs is highly regulated in different cells; whereas impaired expression of different miRNAs has reported in different human disorders, such as cancer. Alteration in expression of miRNAs could be used as prognostic and diagnostic biomarkers. Moreover, numerous miRNAs have been detected that involved in proliferation and migration of human cancer cells through targeting multiple genes [15], [16]. The target genes of miRNAs are mostly recognized as oncogenes and that suppress by

Conclusion

In conclusion, our study suggested that miR‐330 replacement may is a promising strategy for combat against PC cancer cells. We demonstrated that expression of miR-330 significantly downregulated in patients with PC. Our results indicated that restoration of miR-330 expression inhibits proliferation, viability, invasion, and migration of the PC cell line. However, further studies are required to clarify accurate role of miR-330 in PC cells as well as tumor-suppressive mechanisms.

CRediT authorship contribution statement

Reza Mosaed: Validation, Formal analysis, Data curation. Arash Poursheikhani: Methodology, Data curation. Arezoo Farhadi: Writing – original draft, Methodology, Data curation. Mohsen Rajaeinejad: Writing – original draft, Validation, Formal analysis, Data curation. Mohammad Foad Heidari: Software, Investigation, Data curation. Shiva Khalil-Moghaddam: Writing – review & editing, Validation, Investigation, Conceptualization. Peyman Aslani: Writing – review & editing, Software, Formal analysis,

Declaration of Competing Interest

All authors have no conflict of interest to declare.

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