CircRNA hsa_circ_100395 regulates miR-1228/TCF21 pathway to inhibit lung cancer progression

Daishi Chen1,2, Wei Ma3, Zhaoyang Ke1

  • 1a Department of Otolaryngology , The 2nd Clinical Medicine College (Shenzhen People's Hospital) of Jinan University , Shenzhen , China.

Insights

Circular RNA (circRNA) hsa_circ_100395 is decreased in lung cancer, inhibiting tumor growth and metastasis. This study reveals hsa_circ_100395 regulates lung cancer via the miR-1228/TCF21 pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Circular RNAs (circRNAs) are implicated in various cancers, but their role in negatively regulating lung cancer progression is not fully understood.
  • Previous studies have identified some circRNAs involved in lung cancer, yet a comprehensive understanding of their regulatory mechanisms is lacking.

Purpose of the Study:

  • To investigate the role of hsa_circ_100395 in lung cancer development and its underlying molecular mechanisms.
  • To determine if hsa_circ_100395 acts as a tumor suppressor in lung cancer.

Main Methods:

  • Expression analysis of hsa_circ_100395 in lung cancer tissues and correlation with clinical parameters.
  • In vitro assays (cell proliferation, cell-cycle, migration, invasion) and in vivo xenograft experiments to assess the functional role of hsa_circ_100395.
  • Mechanistic studies involving RNA fluorescence in situ hybridization (RNA-FISH), quantitative real-time PCR (qRT-PCR), and rescue assays to elucidate the regulatory pathway.

Main Results:

  • hsa_circ_100395 expression was significantly decreased in lung cancer tissues and inversely correlated with TNM stage and metastasis.
  • Low hsa_circ_100395 expression predicted poor prognosis in lung cancer patients.
  • Overexpression of hsa_circ_100395 inhibited lung cancer cell proliferation, arrested cell cycle, and reduced migration and invasion in vitro, while delaying tumor growth in vivo.
  • hsa_circ_100395 functions as a molecular sponge for miR-1228, targeting TCF21, and this axis regulates lung cancer progression.

Conclusions:

  • hsa_circ_100395 acts as a tumor suppressor in lung cancer.
  • The novel regulatory loop hsa_circ_100395/miR-1228/TCF21 axis plays a crucial role in modulating lung cancer development.
  • hsa_circ_100395 holds potential as a therapeutic target for lung cancer treatment.

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