MicroRNA-138 Abates Fibroblast Motility With Effect on Invasion of Adjacent Cancer Cells

Saroj Rajthala; Himalaya Parajuli; Harsh Nitin Dongre; Borghild Ljøkjel; Kristin Marie Hoven; Arild Kvalheim; Stein Lybak; Evelyn Neppelberg; Dipak Sapkota; Anne Christine Johannessen; Daniela-Elena Costea

doi:10.3389/fonc.2022.833582

MicroRNA-138 Abates Fibroblast Motility With Effect on Invasion of Adjacent Cancer Cells

Front Oncol. 2022 Mar 17:12:833582. doi: 10.3389/fonc.2022.833582. eCollection 2022.

Authors

Saroj Rajthala^{1

2}, Himalaya Parajuli^{1

2}, Harsh Nitin Dongre^{1

2}, Borghild Ljøkjel³, Kristin Marie Hoven³, Arild Kvalheim⁴, Stein Lybak³, Evelyn Neppelberg^{3

5}, Dipak Sapkota⁶, Anne Christine Johannessen^{1

7}, Daniela-Elena Costea^{1

2

7}

Affiliations

¹ The Gade Laboratory for Pathology, Department of Clinical Medicine, Faculty of Medicine, University of Bergen, Bergen, Norway.
² Centre for Cancer Biomarkers (CCBIO), Faculty of Medicine, University of Bergen, Bergen, Norway.
³ Head and Neck Clinic, Haukeland University Hospital, Bergen, Norway.
⁴ Tannteam Private Dental Practice, Bergen, Norway.
⁵ Department of Oral Surgery, Institute of Clinical Dentistry, University of Bergen, Bergen, Norway.
⁶ Department of Oral Biology, University of Oslo, Oslo, Norway.
⁷ Department of Pathology, Haukeland University Hospital, Bergen, Norway.

Abstract

Background: Recent studies have shown aberrant expression of micro-RNAs in cancer-associated fibroblasts (CAFs). This study aimed to investigate miR-138 dysregulation in CAFs in oral squamous cell carcinoma (OSCC) and its effects on their phenotype and invasion of adjacent OSCC cells.

Methods: Expression of miR-138 was first investigated in OSCC lesions (n = 53) and OSCC-derived CAFs (n = 15). MiR-138 mimics and inhibitors were used to functionally investigate the role of miR-138 on CAF phenotype and the resulting change in their ability to support OSCC invasion.

Results: Expression of miR-138 showed marked heterogeneity in both OSCC tissues and cultured fibroblasts. Ectopic miR-138 expression reduced fibroblasts' motility and collagen contraction ability and suppressed invasion of suprajacent OSCC cells, while its inhibition resulted in the opposite outcome. Transcript and protein examination after modulation of miR-138 expression showed changes in CAF phenotype-specific molecules, focal adhesion kinase axis, and TGFβ1 signaling pathway.

Conclusions: Despite its heterogeneous expression, miR-138 in OSCC-derived CAFs exhibits a tumor-suppressive function.

Keywords: cancer-associated fibroblasts; heterogeneity; invasion; motility; oral cancer.